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WO1999031251A1 - Procedes et moyens de production de vecteurs de lentivirus de recombinaison surs et a titre eleve - Google Patents

Procedes et moyens de production de vecteurs de lentivirus de recombinaison surs et a titre eleve Download PDF

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Publication number
WO1999031251A1
WO1999031251A1 PCT/US1998/025719 US9825719W WO9931251A1 WO 1999031251 A1 WO1999031251 A1 WO 1999031251A1 US 9825719 W US9825719 W US 9825719W WO 9931251 A1 WO9931251 A1 WO 9931251A1
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Prior art keywords
lentivirus
vector
ltr
packaging
cell
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PCT/US1998/025719
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WO1999031251A9 (fr
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Luigi Naldini
Thomas Dull
Deborah A. Farson
Rochelle Witt
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Cell Genesys, Inc.
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Priority to AU18034/99A priority Critical patent/AU751985B2/en
Priority to CA2314609A priority patent/CA2314609C/fr
Priority to DE69838758T priority patent/DE69838758T2/de
Priority to JP2000539150A priority patent/JP4640742B2/ja
Priority to KR1020007006425A priority patent/KR20010033064A/ko
Priority to EP98962894A priority patent/EP1036182B1/fr
Publication of WO1999031251A1 publication Critical patent/WO1999031251A1/fr
Publication of WO1999031251A9 publication Critical patent/WO1999031251A9/fr

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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
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    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/11011—Alpharetrovirus, e.g. avian leucosis virus
    • C12N2740/11041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/11044—Chimeric viral vector comprising heterologous viral elements for production of another viral vector
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/16043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16051—Methods of production or purification of viral material
    • C12N2740/16052—Methods of production or purification of viral material relating to complementing cells and packaging systems for producing virus or viral particles

Definitions

  • the invention relates to novel lentiviral packaging vectors, " transfer vectors carrying a foreign gene of interest, stable packaging cell lines, stable producer cell lines and the use thereof for producing recombinant lentivirus in mammalian cells.
  • Retrovirus vectors are a common tool for gene delivery (Miller, Nature (1992) 357:455-460). The ability of retrovirus vectors to deliver an unrearranged, single copy gene into a broad range of rodent, primate and human somatic cells makes retroviral vectors well suited for transferring genes to a cell.
  • a useful adjunct for producing recombinant retroviral vectors are packaging cell lines which supply in trans the proteins necessary for producing infectious virions, but those cells are incapable of packaging endogenous viral genomic nucleic acids (Watanabe & Temin, Molec. Cell. Biol. (1983) 3(12) .2241-2249; Mann et al. , Cell (1983) 33:153-159; E bretson & Te in, J. Virol. (1987) 61(9) :2675-2683) .
  • One approach to minimize the likelihood of generating RCR in packaging cells is to divide the packaging functions into two genomes, for example, one which expresses the gag and pol gene products and the other which expresses the env gene product (Bosselman et al. , Molec. Cell. Biol. (1987) 7 (5) : 1797-1806 ; Markowitz et al., J. Virol. (1988) 62 (4) : 1120-1124 ; Danos & Mulligan, Proc. Natl. Acad. Sci. (1988) 85:6460-6464). That approach minimizes the ability for co-packaging and subsequent transfer of the two-genomes, as well as significantly decreasing the frequency of recombination due to the presence of three retroviral genomes in the packaging cell to produce RCR.
  • Mulligan, supra or deletions (Boselman et al., supra; Markowitz et al., supra) can be configured within the undesired gene products to render any possible recombinants non-functional.
  • deletion of the 3' LTR on both packaging constructs further reduces the ability to form functional recombinants.
  • Lentiviruses are complex retroviruses which, in addition to the common retroviral genes gag, pol and env, contain other genes with regulatory or structural function. The higher complexity enables the lentivirus to modulate the life cycle thereof, as in the course of latent infection.
  • HIV human immunodeficiency virus
  • MDM monocyte-derived macrophages
  • HeLa-Cd4 HeLa-Cd4
  • T ly phoid cells arrested in the cell cycle by treatment with aphidicolin or 7 irradiation.
  • Infection of cells is dependent on the active nuclear import of HIV preintegration complexes through the nuclear pores of the target cells. That occurs by the interaction of multiple, partly redundant, molecular determinants in the complex with the nuclear import machinery of the target cell.
  • Identified determinants include a functional nuclear localization signal (NLS) in the gag matrix (MA) protein, "the karyophilic virion-associated protein, vpr, and a C-terminal phosphotyrosine residue in the gag MA protein.
  • the instant invention relates to novel disarmed lentiviral vectors that direct the synthesis of both lentiviral vector transcripts which can be packaged and lentiviral proteins for rapid production of high titer recombinant lentivirus in mammalian cells.
  • the results are infectious particles for delivering a foreign gene of interest to a target cell.
  • the invention also provides cell lines for virus production.
  • Figure 1 depicts various lentivirus vectors.
  • RSV is the Rous sarcoma virus enhancer/promoter;
  • R is the R region of the LTR;
  • U5 is the U5 region of the LTR;
  • SD is a slice donor site, such as the HIV 5' major splice donor site; is the Psi encapsidation signal sequence;
  • Ga is a part of the gag gene;
  • RRE is the rev responsive element;
  • SA is a splice acceptor sequence; and
  • U3 is the U3 region of the LTR.
  • FIG. 2 depicts additional lentivirus vectors.
  • CMV is cytomegalovirus . Otherwise, the symbols are as found in the legend to Figure 1.
  • Figure 3 is a graph depicting graded vector production with increasing amounts of transfer vector.
  • the instant invention provides a recombinant lentivirus capable of infecting non-dividing cells as well as methods and means for making same.
  • the virus is useful for the in vivo and ex vivo transfer and expression of nucleic acid sequences.
  • the lentiviral genome and the proviral DNA have the three genes found in retroviruses : gag, pol and env, which are flanked by two long terminal repeat (LTR) sequences.
  • the gag gene encodes the internal structural (matrix, capsid and nucleocapsid) proteins; the pol gene encodes the RNA-directed DNA polymerase (reverse transcriptase) , a protease and an integrase; and the env gene encodes viral envelope glycoproteins.
  • the 5' and 3' LTR's serve to promote transcription and polyadenylation of the virion RNA's.
  • the LTR contains all other cis-acting sequences necessary for viral replication.
  • Lentiviruses have additional genes including vif, vpr, tat, rev, vpu, nef and vpx (in HIV-l, HIV-2 and/or SIV) .
  • Adjacent to the 5' LTR are sequences necessary for reverse transcription of the genome (the tRNA primer binding site) and for efficient encapsidation of viral RNA into particles (the Psi site) . If the sequences necessary for encapsidation (or packaging of retroviral RNA into infectious virions) are missing from the viral genome, the cis defect prevents encapsidation of genomic RNA.
  • the invention provides a method of producing a recombinant lentivirus capable of infecting a non-dividing cell comprising transfecting a suitable host cell with two or more vectors carrying the packaging functions, namely gag, pol and env, as well as rev and tat.
  • vectors lacking a functional tat gene are desirable for certain applications.
  • a first vector can provide a nucleic acid encoding a viral gag and a viral pol and another vector can provide a nucleic acid encoding a viral env to produce a packaging cell.
  • Introducing a vector providing a heterologous gene, herein identified as a transfer vector, into that packaging cell yields a producer cell which releases infectious viral particles carrying the foreign gene of interest.
  • the vectors per se, outside of the newly constructed vectors disclosed herein, are known in the art, see Naldini et al., Sci. (1996) 272:263-267; and Zufferey et al., Nat. Biotech. (1997) 15:871-875.
  • the vectors are plasmid-based or virus-based, and are configured to carry the essential sequences for incorporating foreign nucleic acid, for selection and for transfer of the nucleic acid into a host cell.
  • the gag, pol and env genes of the vectors of interest also are known in the art. Thus, the relevant genes are cloned into the selected vector and then used to transform the target cell of interest.
  • the second vector can provide a nucleic acid encoding a viral envelope (env) gene.
  • the env gene can be derived from any virus, including retroviruses .
  • the env preferably is an amphotropic envelope protein which allows transduction of cells of human and other species. W wO v . 9 ? 9- / .3o1 i 25s1t PCT/US98/25719
  • Retroviral vectors can be made target-specific by inserting, for example, a glycolipid or a protein. Targeting often is accomplished by using " an antigen-binding portion of an antibody or a recombinant antibody-type molecule, such as a single chain antibody, to target the retroviral vector.
  • retroviral-derived env genes include, but are not limited to: Moloney murine leukemia virus (MoMuLV or MMLV) , Harvey murine sarcoma virus (HaMuSV or HSV) , murine mammary tumor virus (MuMTV or MMTV) , gibbon ape leukemia virus (GaLV or GALV) , human immunodeficiency virus (HIV) and Rous sarcoma virus (RSV) .
  • Other env genes such as Vesicular stomatitis virus (VSV) protein G (VSV G) , that of hepatitis viruses and of influenza also can be used.
  • VSV Vesicular stomatitis virus
  • VSV G Vesicular stomatitis virus
  • the vector providing the viral env nucleic acid sequence is associated operably with regulatory sequences, e.g., a promoter or enhancer.
  • the regulatory sequence can be any eukaryotic promoter or enhancer, including for example, the Moloney murine leukemia virus promoter-enhancer element, the human cytomegalovirus enhancer or the vaccinia P7.5 promoter. In some cases, such as the Moloney murine leukemia virus promoter-enhancer element, the promoter-enhancer elements are located within or adjacent to the LTR sequences.
  • the regulatory sequence is one which is not endogenous to the lentivirus from which the vector is being constructed. Thus, if the vector is being made from SIV, the SIV regulatory sequence found in the SIV LTR would be replaced by a regulatory element which does not originate from SIV.
  • VSV G protein is a desirable env gene because VSV G confers broad host range on the recombinant virus, VSV G can be deleterious to the host cell.
  • VSV G can be deleterious to the host cell.
  • the tetracycline-regulatable gene expression system of Gossen & Bujard can be employed to provide for inducible expression of VSV G when tetracycline is withdrawn from the transferred cell.
  • the tet/VP16 transactivator is present on a first vector and the VSV G coding sequence is cloned downstream from a promoter controlled by tet operator sequences on another vector.
  • heterologous or foreign nucleic acid sequence is linked operably to a regulatory nucleic acid sequence.
  • heterologous nucleic acid sequence refers to a sequence that originates from a foreign species, or, if from the same species, it may be substantially modified from the original form. Alternatively, an unchanged nucleic acid sequence that is not expressed normally in a cell is a heterologous nucleic acid sequence.
  • operably linked refers to functional linkage between a regulatory sequence and a heterologous nucleic acid sequence resulting in expression of the latter.
  • the heterologous sequence is linked to a promoter, resulting in a chimeric gene.
  • the heterologous nucleic acid sequence is preferably under control of either the viral LTR promoter-enhancer signals or of an internal promoter, and retained signals within the retroviral LTR can still bring about efficient expression of the transgene.
  • the foreign gene can be any nucleic acid of interest which can be transcribed. Generally the foreign gene encodes 'a polypeptide. Preferably the polypeptide has some therapeutic benefit. The polypeptide may supplement deficient or nonexistent expression of an endogenous protein in a host cell. The polypeptide can confer new properties on the host cell, such as a chimeric signalling receptor, see U.S. Patent No. 5,359,046. The artisan can determine the appropriateness of a foreign gene practicing techniques taught herein and known in the art. For example, the artisan would know whether a foreign gene is of a suitable size for encapsidation and whether the foreign gene product is expressed properly.
  • a gene regulating molecule in a cell by the introduction of a molecule by the method of the invention.
  • modulate envisions the suppression of expression of a gene when it is over-expressed or augmentation of expression when it is under-expressed.
  • nucleic acid sequences that interfere with the expression of a gene at the translational level can be used.
  • the approach can utilize, for example, antisense nucleic acid, ribozymes or triplex agents to block transcription or translation of a specific mRNA, either by masking that mRNA with an antisense nucleic acid or triplex agent, or by cleaving same with a ribozyme.
  • Antisense nucleic acids are DNA or RNA molecules which are complementary to at least a portion of a specific" mRNA molecule (Weintraub, Sci. Am. (1990) 262:40). In the cell, the antisense nucleic acids hybridize to the corresponding mRNA forming a double-stranded molecule.
  • antisense nucleic acids interfere with the translation of the mRNA since the cell will not translate a mRNA that is double-stranded.
  • Antisense oligomers of about 15 nucleotides or more are preferred since such are synthesized easily and are less likely to cause problems than larger molecules when introduced into the target cell.
  • the use of antisense methods to inhibit the in vitro translation of genes is well known in the art
  • the antisense nucleic acid can be used to block expression of a mutant protein or a dominantly active gene product, such as amyloid precursor protein that accumulates in Alzheimer's disease. Such methods are also useful for the treatment of Huntington's disease, hereditary Parkinsonism and other diseases. Antisense nucleic acids are also useful for the inhibition of expression of proteins associated with toxicity.
  • oligonucleotide to stall transcription can be by the mechanism known as the triplex strategy since the oligomer winds around double-helical DNA, forming a three-strand helix. Therefore, the triplex compounds can be designed to recognize a unique site on a chosen gene (Maher et al., Antisense Res and Dev. (1991) 1(3):227; Helene, Anticancer Drug Dis. (1991) 6(6):569).
  • Ribozymes are RNA molecules possessing the ability to specifically cleave other single-stranded RNA in a manner analogous to DNA restriction endonucleases. Through the modification of nucleotide sequences which encode those RNA's, it is possible to engineer molecules that recognize and cleave specific nucleotide sequences in an RNA molecule (Cech, J. Amer. Med Assn. (1988) 260:3030)'. A major advantage of that approach is only mRNA's with particular sequences are inactivated.
  • nucleic acid encoding a biological response modifier.
  • immunopotentiating agents including nucleic acids encoding a number of the cytokines classified as "interleukins” , for example, interleukins 1 through 12.
  • interferons include gamma interferon (7-IFN) , tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF) . It may be desirable to deliver such nucleic acids to bone marrow cells or macrophages to treat inborn enzymatic deficiencies or immune defects.
  • Nucleic acids encoding growth factors, toxic peptides, ligands, receptors or other physiologically important proteins also can be introduced into specific non-dividing cells.
  • the recombinant lentivirus of the invention can be used to treat an HIV-infected cell (e.g., T-cell or macrophage) with an an i-HIV molecule.
  • an HIV-infected cell e.g., T-cell or macrophage
  • respiratory epithelium for example, can be infected with a recombinant lentivirus of the invention having a gene for cystic fibrosis transmembrane conductance regulator
  • CTR cystic fibrosis
  • the method of the invention may also be useful for neuronal, glial, fibroblast or mesenchymal cell transplantation, or "grafting", which involves transplantation of cells infected with the recombinant lentivirus of the invention ex vivo, or infection in vivo into the central nervous system or into the ventricular cavities or subdurally onto the surface of a host brain.
  • grafting Such methods for grafting will be known to those skilled W wO ⁇ 9 y 9 y / / 3o1 i 2.s51 i PCT JS98/25719
  • gene transfer could introduce a normal gene into the affected tissues for replacement therapy, as well as to create animal models for the disease using antisense mutations.
  • a Factor VIII or IX encoding nucleic acid into a lentivirus for infection of a muscle, spleen or liver cell.
  • the promoter sequence may be homologous or heterologous to the desired gene sequence.
  • a wide range of promoters may be utilized, including a viral or a mammalian promoter.
  • Cell or tissue specific promoters can be utilized to target expression of gene sequences in specific cell populations. Suitable mammalian and viral promoters for the instant invention are available in the art.
  • the nucleic acid construct referred to as the transfer vector having the packaging signal and the heterologous cloning site, also contains a selectable marker gene.
  • Marker genes are utilized to assay for the presence of the vector, and thus, to confirm infection and integration. The presence of a marker gene ensures the selection and growth of only those host cells which express the inserts.
  • Typical selection genes encode proteins that confer resistance to antibiotics and other toxic substances, e.g., histidinol, puromycin, hygromycin, neomycin, methotrexate etc. and cell surface markers.
  • nucleic acid sequence refers to any nucleic acid molecule, preferably DNA, as discussed in detail herein.
  • the nucleic acid molecule may be derived from a variety of sources, including DNA, cDNA, synthetic DNA, RNA or combinations thereof.
  • Such nucleic acid sequences may comprise genomic DNA which may or may not include naturally occurring introns.
  • genomic DNA may be obtained in association with promoter regions, poly A sequences or other associated sequences. Genomic DNA may be extracted and purified from suitable cells by means well known in the art. Alternatively, messenger RNA (mRNA) can be isolated from cells and used to produce cDNA by reverse transcription or other means.
  • mRNA messenger RNA
  • the recombinant lentivirus produced by the method of the invention is a derivative of human immunodeficiency virus (HIV) .
  • HIV human immunodeficiency virus
  • the env will be derived from a virus other than HIV.
  • the method of the invention provides, in some embodiments, three vectors which provide all of the functions required for packaging of recombinant virions, such as, gag, pol, env, tat and rev, as discussed above.
  • tat may be deleted functionally for unexpected benefits.
  • the vectors are introduced via transfection or infection into the packaging cell line.
  • the packaging cell line produces viral particles that contain the vector genome. Methods for transfection or infection are well known by those of skill in the art. After cotransfection of the packaging vectors and the transfer vector to the packaging cell line, the recombinant virus is recovered from the culture media and titered by standard methods used by those of skill in the art.
  • the packaging constructs can be introduced into human cell lines by calcium phosphate transfection, lipofection or electroporation, generally together with a dominant selectable marker, such as neo, DHFR, Gin synthetase or ADA, followed by selection in the presence of the appropriate drug and isolation of clones.
  • the selectable marker gene can be linked physically to the packaging genes in the construct.
  • Stable cell lines wherein the packaging functions are configured to be expressed by a suitable packaging cell are known. For example, see U.S. Pat. No. 5,686,279; and
  • the construct contains tat and rev sequences and the 3' LTR is replaced with poly A sequences.
  • the 5' LTR and psi sequences are replaced by another promoter, such as one which is inducible.
  • a CMV promoter or derivative thereof can be used.
  • the packaging vectors of interest contain additional changes to the packaging functions to enhance lentiviral protein expression and to enhance safety. For example, all of the HIV sequences upstream of gag can be removed. Also, sequences downstream of env can be removed.
  • steps can be taken to modify the vector to enhance the splicing and translation of the RNA.
  • the instant invention provides for lentivirus packaging plasmids wherein tat sequences, a regulating protein which promotes viral expression through a transcriptional mechanism, are deleted functionally.
  • tat sequences a regulating protein which promotes viral expression through a transcriptional mechanism
  • the tat gene can be deleted, in part or in whole, or various point mutations or other mutations can be made to the tat sequence to render the gene non-functional.
  • An artisan can practice known techniques to render the tat gene non-functional.
  • Isolated plasmids, DNA sequences or synthesized oligonucleotides are cleaved, tailored and religated in the form desired.
  • Site-specific DNA cleavage is performed by treating with the suitable restriction enzyme (or enzymes) under conditions which are understood in the art, and the particulars of which are specified by the manufacturer of the commercially available restriction enzymes, see, e.g. New England Biolabs, Product Catalog.
  • suitable restriction enzyme or enzymes
  • about 1 ⁇ g of plasmid or DNA sequences is cleaved by one unit of enzyme in about 20 ⁇ l of buffer solution.
  • an excess of restriction enzyme is used to ensure complete digestion of the DNA substrate. Incubation times of about one hour to two hours at about 37 °C are workable, although variations can be tolerated.
  • cleaved fragments After each incubation, protein is removed by extraction with phenol/chloroform, which may be followed by ether extraction, and the nucleic acid recovered from aqueous fractions by precipitation with ethanol. If desired, size separation of the cleaved fragments may be performed by polyacrylamide gel or agarose gel electrophoresis using standard techniques. A general description of size separations is found in Methods of Enzymology 65:499-560 (1980) .
  • Restriction cleaved fragments may be blunt ended by treating with the large fragment of E. coli DNA polymerase I (Klenow) in the presence of the four deoxynucleotide triphosphates (dNTP's) using incubation times of about 15 to 25 minutes at 20°C in 50 mM Tris (pH 7.6) " 50 mM NaCl, 6 mM MgCl 2 , 6 mM DTT and 5-10 ⁇ M dNTP's.
  • the Klenow fragment fills in at 5' sticky ends but chews back protruding 3' single strands, even though the four dNTP's are present.
  • selective repair can be performed by supplying only one of the dNTP's, or with selected dNTP's, within the limitations dictated by the nature of the sticky ends.
  • the mixture is extracted with phenol/chloroform and ethanol precipitated.
  • Treatment under appropriate conditions with SI nuclease or Bal-31 results in hydrolysis of any single-stranded portion.
  • Ligations can be performed in 15-50 ⁇ l volumes under the following standard conditions and temperatures: 20 mM Tris-Cl pH 7.5, 10 M MgCl 2 , 10 mM DTT, 33 mg/ml BSA, 10 mM-50 mM NaCl and either 40 ⁇ M ATP, 0.01-0.02 (Weiss) units T4 DNA ligase at 0°C (for "sticky end” ligation) or 1 mM ATP, 0.3-0.6 (Weiss) units T4 DNA ligase at 14 °C (for "blunt end” ligation) .
  • Intermolecular "sticky end” ligations are usually performed at 33-100 ⁇ g/ml total DNA concentrations (5-100 mM total end concentration) .
  • Intermolecular blunt end ligations (usually employing a
  • a lentiviral packaging vector is made to contain a promoter and other optional or requisite regulatory sequences as determined by the artisan, gag, pol, rev, env or a combination thereof, and with specific functional or actual excision of tat, and optionally other lentiviral accessory genes.
  • the integrated lentiviral vector In transduced cells, the integrated lentiviral vector generally has an LTR at each termini.
  • the 5' LTR may cause accumulation of "viral" transcripts that may be the substrate of recombination, in particular in HIV-infected cells.
  • the 3' LTR may promote downstream transcription with the consequent risk of activating a cellular protooncogene.
  • the U3 sequences comprise the majority of the HIV LTR.
  • the U3 region contains the enhancer and promoter elements that modulate basal and induced expression of the HIV genome in infected cells and in response to cell activation.
  • Several of the promoter elements are essential for viral replication. Some of the enhancer elements are highly conserved among viral isolates and have been implicated as critical virulence factors in viral pathogenesis. The enhancer elements may act to influence replication rates in the different cellular target of the virus (Marthas et al. J. Virol. (1993) 67:6047-6055) .
  • the 3 ' LTR acts as template for the generation of both LTR's in the integrated provirus. If the 3' copy of the U3 region is altered in a retroviral vector construct, the vector RNA still is produced from the intact 5' LTR in producer cells, but cannot be regenerated in target cells.
  • the retrovirus is sel -inactivating (SIN) and those vectors are known as Sin transfer vectors.
  • the 5' end of the U3 region serves another essential function in vector transfer, being required for integration (terminal dinucleotide + att sequence).
  • the terminal dinucleotide and the att sequence may represent the 5' boundary of the U3 sequences which can be deleted.
  • some loosely defined regions may influence the activity of the downstream polyadenylation site in the R region. Excessive deletion of U3 sequence from the 3' LTR may decrease polyadenylation of vector transcripts with adverse consequences both on the titer of the vector in producer cells and the transgene expression in target cells. On the other hand, limited deletions may not abrogate the transcriptional activity of the LTR in transduced cells.
  • New versions of a lentivirus transfer vector described herein carry increasing deletions of the U3 region of the 3' LTR ( Figure 1: the U3 deletions span from nucleotide -418 of the U3 LTR to the indicated position: SIN-78,
  • Lentiviral vectors with almost complete deletion of the U3 sequences from the 3 ' LTR were developed without compromising either the titer of vector in producer cells or transgene expression in target cells.
  • the most extensive deletion (-418 to -18) extends as far as to the TATA box, therefore abrogating any transcriptional activity of the LTR in transduced cells.
  • the lower limit of the 3' deletion may extend as far as including the TATA box.
  • the deletion may be of the remainder of the U3 region up to the R region.
  • the average expression level of the transgene was even higher in cells transduced by the SIN vectors as compared to more intact vectors. That was probably due to the removal of transcriptional interference from the upstream HIV LTR on the internal promoter. SIN-type vectors with such extensive deletions of the U3 region could not be generated for murine leukemia virus (MLV) based retroviral vectors without compromising efficiency of transduction.
  • MLV murine leukemia virus
  • the 5' LTR of transfer vector construct was modified by substituting part or all of the transcriptional regulatory elements of the U3 region with heterologous enhancer/promoters. The changes were made to enhance the expression of transfer vector RNA in producer cells; to allow vector production in the absence of the HIV tat gene; and to remove the upstream wild-type copy of the HIV LTR that can recombine with the 3' deleted version to "rescue" the above described SIN vectors.
  • vectors containing the above-described alterations at the 5' LTR, 5' vectors can find use as transfer vectors because of the sequences to enhance expression and in combination with packaging cells that do not express tat.
  • LTR as discussed hereinabove to yield improved transfer vectors which have not only enhanced expression and can be used in packaging cells that do not express tat but can be self-inactivating as well.
  • the transcription from the HIV LTR is highly dependent on the transactivator function of the tat protein.
  • vector transcription from the HIV LTR is stimulated strongly.
  • full-length "viral" RNA has a full complement of packaging signals, the RNA is encapsidated efficiently into vector particles and transferred to target cells.
  • the amount of vector RNA available for packaging in producer cells is a rate-limiting step in the production of infectious vector.
  • the enhancer or the enhancer and promoter regions of the 5' LTR were substituted with the enhancer or the enhancer and promoter of the human cytomegalovirus (CMV) or murine Rous sarcoma virus (RSV) , respectively, see Figure 2 for a schematic of the constructs and the code names of the hybrid vectors.
  • CCL and RRL vectors have complete substitution of the 5' U3 region.
  • control lentivector HR2 and the panel of 5' hybrids were compared in producer cells tran ⁇ fected with the transfer vector, and with or without packaging constructs, which provide the tat transactivator.
  • the transcriptional level of the four chimeric vectors is higher than that of a control lentivector both in the presence and in the absence of the packaging construct. All chimeric vectors efficiently transfer the transgene into target cells and the RRL vector performs as well as the control HR2 vector.
  • integration of the vector in target cells was confirmed by examining transduced cells at an early and a later passage after transduction. No decrease was observed in the percentage of transgene-positive cells indicating that the vector had been integrated.
  • a lentiviral vector of significantly improved biosafety is a SIN transfer vector that has no wild-type copy of the HIV LTR either at the 5' or at the 3' end, which is used in conjunction with tat-less packaging vectors as described herein.
  • Viral supernatants are harvested using standard techniques such as filtration of supernatants 48 hours post transfection.
  • the viral titer is determined by infection of, for example, 10 6 NIH 3T3 cells or 10 5 HeLa cells with an appropriate amount of viral supernatant, in the presence of 8 ⁇ g/ml polybrene (Sigma Chemical Co., St. Louis, MO) . Forty-eight hours later, the transduction efficiency is assayed.
  • the instant invention provides methods and means for producing high titer recombinant virus.
  • Those virus particle preparations can be used to infect target cells using techniques known in the art.
  • the instant invention will find use in ex vivo gene therapy applications wherein target cells are removed from a host, transformed in culture practicing known techniques and then returned to the host.
  • the lentiviral packaging plasmids were derived from the plasmid pCMV ⁇ R8.9 ( ⁇ Vpr ⁇ Vif ⁇ Vpu ⁇ Nef) described previously in Zufferey et al., supra. All the remaining sequences of the nef gene in pCMV ⁇ R8.9 were removed by digesting with Xhol and BstEII, filing in with Klenow and religating. The construction deleted 100 basepairs, joining the truncated env reading frame of HIV-1 to the genomic insulin polyadenylation site and yielding the plasmid pCMV ⁇ R8.73.
  • 133 basepairs of CMV-derived sequences downstream of the CMV promoter were deleted in the plasmid pCMV ⁇ R8.73. That sequence contains a splice donor site and it was removed by digestion of the plasmid pCMV ⁇ R8.73 with SacII and religation of the larger fragment, obtaining the plasmid pCMV ⁇ R8.74.
  • pCMV ⁇ R8.75 was derived from pCMV ⁇ R8.74 by replacing the 94 bp Sstll-Clal fragment with an Sstll-Clal oligonucleotide linker consisting of, 5'-
  • an inducible packaging construct was obtained by replacing the Pstl-SacII fragment of pCMV ⁇ R8.74 containing the CMV promoter with seven tandem copies of the tetracycline operator sequences linked to a minimal CMV promoter.
  • the tet-regulated packaging plasmid pTet ⁇ R8.74 was obtained.
  • the lentiviral transfer vector plasmids were derived from the plasmid pHR'-CMV-LacZ described previously in Naldini et al. (Sci. (1996) 272:263-267).
  • pHR2 is a lentiviral transfer vector in which 124 bp of nef sequences upstream of the 3' LTR in pHR' were replaced with a polylinker both to reduce HIV1 sequences and to facilitate transgene cloning.
  • pHR2 was derived from pHR'-CMV-LacZ by replacing the 4.6 kb Clal-StuI fragment with the 828 bp Clal-StuI fragment generated by PCR using pHR'-CMV-LacZ as the template and the oligonucleotide, 5'- CCATCGATCACGAGACTAGTCCTACGTATCCCCGGGGACGGGATCCGCGGAATTCC GTTTAAGAC-3' (SEQ ID NO: ) and 5 ' -TTATAATGTCAAGGCCTCTC-3 ' (SEQ ID NO: ) in a three part ligation with a 4.4 kb
  • pHR3 is a lentiviral transfer vector in which 148 bp of env coding sequences (including an ATG) upstream of the Rev Response Element (RRE) in pHR2 were deleted.
  • pHR3 was derived from pHR2 by replacing the 893 bp Notl-Spel fragment of 'pHR2 with a 747 bp Notl-Spel fragment generated by PCR using pHR2 as the template with oligonucleotide primers 5'- GCGGCCGCAGGAGCTTTGTTCCTTGG-3 ' (SEQ ID NO: ) and 5'-
  • pHR5 is a lentiviral transfer vector in which 310 bp gag coding sequences (all gag coding sequences downstream from amino acid 15 of the Gag protein) were deleted from pHR2.
  • pHR5 was derived by digestion of pHR2 with Nrul, addition of a NotI linker (synthetic oligonucleotide 5 ' -TTGCGGCCGCAA-3 ' ,
  • pHR6 is a lentiviral vector in which the 5' splice donor signal was mutated (TGGT to TGAT) to enhance production of full-length transcripts capable of being packaged. pHR6 was derived from pHR5 by replacing the 239 bp Aflll-Apol fragment with a 239 bp Aflll-Apol fragment generated by
  • PCR fragments were generated by first cloning the PCR reaction product directly into the TA cloning vector pCR2.1 (Invitrogen) followed by sequence verification and excision with the appropriate enzymes.
  • the 5' LTR of the lentiviral vector contains the enhancer and promoter from the U3 region of the Rous Sarcoma Virus (RSV) joined to the R region of HIV-l (plasmid pRRL) .
  • pRRL is a lentiviral transfer vector in which the enhancer and promoter (nucleotides -233 to -1 relative to the transcriptional start site) of RSV is precisely fused to the R region of HIV-1 using an oligonucleotide linker.
  • pRRL was derived from plasmids pRT43.RSV.F3 , see WO97/07225, and pHR2 by replacing the 3.4 kb EcoRI-Hpal fragment of pRT43.RSV.F3 with the .67 kb Bglll-NotI fragment from pHR2 and the 1.7kb Notl-StuI fragment from pHR2 along with a synthetic EcoRI-Bglll oligonucleotide linker consisting of oligonucleotides 5'- AATTGCCGCATTGCAGAGATATTGTATTTAAGTGCCTAGCTCGATACAATAAACGG
  • the 5' LTR of the lentiviral vector contains the enhancer (nucleotides
  • pRLL is a lentiviral transfer vector in which the enhancer of RSV is fused to the promoter region of HIV-1 using an oligonucleotide linker.
  • pRRL was derived from plasmids pRT43.RSV.F3 and pHR2 by replacing the 3.4 kb EcoRI-Hpal fragment of pRT43.RSV.F3 with the .724 kb AlwNI-NotI fragment from pHR2 and the 1.7 kb Notl-StuI fragment from pHR2 along with a synthetic EcoRI-AlwNI oligonucleotide linker consisting of the oligo, 5'- AATTGGAGGCGTGGCCTGGGCGGGACTGGGGAGTGGCGAGCCCTCAGATC-3 ' (SEQ ID NO: ) and the oligonucleotide, 5'- CTGAGGGCTCGCCACTCCCCAGTCCCGCCCAGGCCACGCCTCC-3' (SEQ ID NO:
  • the 5' LTR of the lentiviral vector contains the immediate early enhancer and promoter (nucleotides -673 to -1, relative to the transcriptional start site according to
  • pCCL was derived from plasmids pRT43.2F3 (U.S. Pat. No. 5,686,279) and pHR2 by replacing the 3.8 kb Sstl-Hpal fragment of pRT43.2F3 with the 1.7 kb Bglll-NotI fragment from pHR2 and the 1.7 kb Notl-StuI fragment from pHR2 along with a synthetic Sstl-Bglll oligonucleotide linker consisting of the oligonucleotides , 5'-
  • the 5 'LTR of the lentiviral vector contains the enhancer nucleotides -220 - -673 relative to the transcriptional start site of Cytomegalovirus (CMV) joined to the promoter region (from position -78 bp relative to the transcriptional start site) of HIV-1.
  • CMV Cytomegalovirus
  • pCLL was derived from plasmids pRT43.2F3 and pHR2 by replacing the 3.6 kb Ncol-Hpal fragment of pRT43.2F3 with the .724 kb AlwNI-NotI fragment from pHR2 and the 1.7kb Notl-StuI fragment from pHR2 along with a synthetic NcoI-AlwNI oligonucleotide linker consisting of oligo, 5'- CATGGAGGCGTGGCCTGGGCGGGACTGGGGAGTGGCGAGCCCTCAGATC-3 ' (SEQ
  • pRRL.SIN-18 was derived from pRRL by deleting the 400 bp EcoRV-PvuII fragment in the 3' LTR by digestion and religation.
  • pRRL.SIN-36 was derived from pRRL by replacing the
  • pRRL.SIN-78 was derived from pRRL by replacing the 493 bp BbsI-AlwNI fragment in the 3 'LTR with an oligonucleotide linker consisting of, 5'- GATATGATCAGGAGGCGTGGCCTGGGCGGGACTGGGGAGTGGCGAGCCCTCAGATC-
  • the 293G cell line was used to generate stable lentiviral packaging cells.
  • 293G cells express the tet R /VP16 transactivator from the MD cassette (CMV promoter and intervening sequences - exons 2 and 3, intron 2- and poly (A) site from the human ⁇ globin gene) and the VSV envelope from a minimal CMV promoter linked to a tandem repeat of seven tetracycline operator sites (tet°) .
  • the expression of VSV G thus is regulated by the level of tetracycline in the culture medium, being suppressed in the presence of the antibiotic (Gossen & Bujard, Proc.
  • the best 5 clones were determined to have p24 values of 12-23 ng/ml. Of the 5 clones, 4 were positive for VSV.G expression after tetracycline withdrawal by Western blot analysis. The four p24/VSV.G positive clones were analyzed further for the ability to package lentiviral transfer vectors.
  • the clones were infected with transiently produced lentiviral vector (VSV.G pseudotype) containing an expression cassette for the Green Fluorescent Protein of A. victoria (GFP) driven by the CMV promoter, at a multiplicity of infection of 10 and in the presence of polybrene (8 ⁇ g/ml) . The infected clones then were expanded and the tetracycline removed.
  • VSV.G pseudotype transiently produced lentiviral vector
  • GFP Green Fluorescent Protein of A. victoria
  • the infected packaging population 10-28, was used for the creation of high titer producer clones of GFP lentiviral vector. 10-28 cells were sorted by FACS and the highest GFP expressing cells were retained and expanded. That population then was infected serially
  • VSV.G pseudotype transiently produced GFP lentiviral
  • the supernatants were collected after a 72-96 hr of VSV.G induction. Supernatants were titered on HeLa cells and analyzed for p24 content by immunocapture assay. Infectious titers peaked after the third ping reaching 1.5 x 10 6 T.U./ml (see Figure 3). The population of cells from the third ping then were subcloned to isolate high titer vector producers.

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Abstract

L'invention porte sur des vecteurs lentiviraux modifiés en LRT 5', ou 5' et 3' servant à produire des vecteurs lentiviraux de recombinaison. Lesdits vecteurs peuvent être produits en l'absence du gène fonctionnel tat. De multiples transformations de la cellule hôte avec le vecteur porteur du transgène renforcent la production des virus.
PCT/US1998/025719 1997-12-12 1998-12-11 Procedes et moyens de production de vecteurs de lentivirus de recombinaison surs et a titre eleve WO1999031251A1 (fr)

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AU18034/99A AU751985B2 (en) 1997-12-12 1998-12-11 Method and means for producing high titer, safe, recombinant lentivirus vectors
CA2314609A CA2314609C (fr) 1997-12-12 1998-12-11 Procedes et moyens de production de vecteurs de lentivirus de recombinaison surs et a titre eleve
DE69838758T DE69838758T2 (de) 1997-12-12 1998-12-11 Verfahren und mittel zur herstellung von sicheren, rekombinanten lentivirusvektoren mit hohem titer
JP2000539150A JP4640742B2 (ja) 1997-12-12 1998-12-11 高力価で安全な組換えレンチウイルスベクター作成の方法及び手段
KR1020007006425A KR20010033064A (ko) 1997-12-12 1998-12-11 높은 역가를 갖는 안전한 재조합 렌티바이러스 벡터를생성시키는 방법 및 수단
EP98962894A EP1036182B1 (fr) 1997-12-12 1998-12-11 Procedes et moyens de production de vecteurs de lentivirus de recombinaison surs et a titre eleve

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Cited By (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000078987A1 (fr) * 1999-06-22 2000-12-28 Dnavec Research Inc. Vecteur d'expression de deux genes etrangers
EP1171624A4 (fr) * 1999-04-29 2002-06-26 Cell Genesys Inc Procede et moyens de production de vecteurs lentiviraux recombinants surs et a titre eleve
WO2002049422A3 (fr) * 2000-12-20 2002-11-14 Leuven K U Res & Dev Modeles de maladies developpes chez des animaux non humains
WO2001091801A3 (fr) * 2000-05-26 2003-02-06 Chiron Corp Procedes de transduction de cellules neuronales cerebelleuses par le biais de vecteurs de lentivirus
US6712612B1 (en) 2000-12-12 2004-03-30 Genecure Llc Safe and stable retroviral helper cell line and related compositions and methods
US6808905B2 (en) 2001-05-14 2004-10-26 Cell Genesys, Inc. Lentiviral vectors encoding clotting factors for gene therapy
WO2006010834A1 (fr) 2004-06-25 2006-02-02 Centre National De La Recherche Scientifique Lentivirus non integratif et non replicatif, preparation et utilisations
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US8846385B2 (en) 1997-12-12 2014-09-30 Gbp Ip, Llc Method and means for producing high titer, safe recombinant lentivirus vectors
US9593340B2 (en) 2007-10-15 2017-03-14 Admedus Vaccines Pty Ltd. Expression system for modulating an immune response
WO2017096432A1 (fr) 2015-12-09 2017-06-15 Admedus Vaccines Pty Ltd Composition immunomodulatrice pour le traitement
WO2017136358A1 (fr) 2016-02-01 2017-08-10 Bioverativ Therapeutics Inc. Gènes du facteur viii optimisés
US9795658B2 (en) 2010-04-20 2017-10-24 Admedus Vaccines Pty Ltd Expression system for modulating an immune response
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WO2018083538A1 (fr) 2016-11-07 2018-05-11 Neuracle Scienc3 Co., Ltd. Anticorps anti- famille avec similarité de séquence 19, élément a5 et leur procédé d'utilisation
WO2019075220A1 (fr) 2017-10-11 2019-04-18 Bioverativ Usa Inc. Procédés permettant d'induire une activité de complément
WO2019152692A1 (fr) 2018-02-01 2019-08-08 Bioverativ Therapeutics, Inc. Utilisation de vecteurs lentiviraux exprimant le facteur viii
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US11560425B2 (en) 2017-06-27 2023-01-24 Neuracle Science Co., Ltd. Use of anti-FAM19A5 antibodies for treating cancers
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US11634484B2 (en) 2018-04-24 2023-04-25 Neuracle Science Co., Ltd. Use of anti-family with sequence similarity 19, member A5 antibodies for the treatment of neuropathic pain
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* Cited by examiner, † Cited by third party
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US6605712B1 (en) * 1990-12-20 2003-08-12 Arch Development Corporation Gene transcription and ionizing radiation: methods and compositions
US7670823B1 (en) 1999-03-02 2010-03-02 Life Technologies Corp. Compositions for use in recombinational cloning of nucleic acids
US5888767A (en) * 1996-11-27 1999-03-30 The Johns Hopkins University School Of Medicine Method of using a conditionally replicating viral vector to express a gene
HUP0000421A2 (hu) 1996-10-17 2000-06-28 Oxford Biomedica (Uk) Limited Retrovirális vektorok
US7198784B2 (en) * 1996-10-17 2007-04-03 Oxford Biomedica (Uk) Limited Retroviral vectors
CA2304983A1 (fr) 1997-09-24 1999-04-01 The Regents Of The University Of California Vecteurs de lentivirus non originaires de primates et systemes d'encapsidation
NZ520579A (en) * 1997-10-24 2004-08-27 Invitrogen Corp Recombinational cloning using nucleic acids having recombination sites and methods for synthesizing double stranded nucleic acids
EP1895010B1 (fr) * 1997-12-22 2011-10-12 Oxford Biomedica (UK) Limited Vecteurs basés sur le virus de l'anémie infectieuse des équidés (vaie)
US6387695B1 (en) * 1997-12-23 2002-05-14 Merck & Co., Inc. DNA pharmaceutical formulations comprising citrate or triethanolamine and combinations thereof
US7262049B2 (en) * 1999-03-16 2007-08-28 Dana-Farber Cancer Institute, Inc. Pseudotyped lentiviral vectors and uses thereof
EP1165842A4 (fr) * 1999-03-16 2004-07-07 Dana Farber Cancer Inst Inc Systeme vectoriel lentiviral pour le criblage de grande quantite
KR100354562B1 (ko) * 1999-12-06 2002-09-30 주식회사 제넥신 원숭이에서 ＳＩＶｍａｃ２３９의 감염에 대한 방어를유도하는 ＡＩＤＳ ＤＮＡ 백신
JP4729222B2 (ja) * 1999-12-10 2011-07-20 ライフ テクノロジーズ コーポレーション 組換えクローニングにおける独自の選択性を有する複数の組換え部位の使用
US6656706B2 (en) * 1999-12-23 2003-12-02 The United States Of America As Represented By The Department Of Health And Human Services Molecular clones with mutated HIV gag/pol, SIV gag and SIV env genes
US20040204379A1 (en) * 2000-06-19 2004-10-14 Cheng Seng H. Combination enzyme replacement, gene therapy and small molecule therapy for lysosomal storage diseases
US20030224415A1 (en) * 2001-06-29 2003-12-04 Gala Design, Inc. Selection free growth of host cells containing multiple integrating vectors
EP1297168A2 (fr) * 2000-07-03 2003-04-02 Gala Design, Inc. Vecteurs d'expression
US6852510B2 (en) 2000-07-03 2005-02-08 Gala Design Inc Host cells containing multiple integrating vectors
US20040235173A1 (en) * 2000-07-03 2004-11-25 Gala Design, Inc. Production of host cells containing multiple integrating vectors by serial transduction
US7198924B2 (en) 2000-12-11 2007-04-03 Invitrogen Corporation Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites
US6800281B2 (en) * 2000-11-09 2004-10-05 Oxford Biomedica (Uk) Limited Lentiviral-mediated growth factor gene therapy for neurodegenerative diseases
US7575924B2 (en) 2000-11-13 2009-08-18 Research Development Foundation Methods and compositions relating to improved lentiviral vectors and their applications
US7122181B2 (en) * 2000-12-19 2006-10-17 Research Development Foundation Lentiviral vector-mediated gene transfer and uses thereof
EP1472337A4 (fr) 2001-03-09 2008-02-27 Univ Texas Induction de l'immunite tumorale par des variantes de la proteine de fixation a folate
NZ527937A (en) * 2001-03-13 2005-03-24 Novartis Ag Stable cell lines to express high levels of lentiviral Gag/Pol proteins for generation of HIV- or BIV- based lentiviral vectors
ES2380007T3 (es) * 2001-04-06 2012-05-07 The University Of Chicago Inducción por agentes quimioterapéuticos de la actividad del promotor Egr-1 en la terapia génica
US20040242523A1 (en) * 2003-03-06 2004-12-02 Ana-Farber Cancer Institue And The Univiersity Of Chicago Chemo-inducible cancer gene therapy
US8034791B2 (en) 2001-04-06 2011-10-11 The University Of Chicago Activation of Egr-1 promoter by DNA damaging chemotherapeutics
US20040033604A1 (en) * 2001-04-20 2004-02-19 Gary Kobinger Recombinant lentiviral vectors pseudotyped in envelopes containing filovirus binding domains
AU2002307393A1 (en) * 2001-04-20 2002-11-05 The Salk Institute For Biological Studies Inducible expression of transfected genes
EP1399541A4 (fr) 2001-05-22 2005-04-13 Univ Chicago Arn polymerase dependant de l'adn a brin unique de virion n4
ITMI20011138A1 (it) * 2001-05-29 2002-11-29 Uni Di Torino Vettore e metodi di impiego per l'espressione selettiva di geni in siti di angiogenesi in vivo
DE60228082D1 (de) 2001-05-31 2008-09-18 Novartis Ag Nten und neue liganden und pharmazeutische zusammensetzungen
WO2003002155A1 (fr) 2001-06-29 2003-01-09 Sloan Kettering Institute For Cancer Research Vecteur codant pour le gene-globine humain et utilisation de celui-ci dans le traitement d'hemoglobinopathies
US7629153B2 (en) * 2001-08-02 2009-12-08 Research Development Foundation Methods and compositions relating to improved lentiviral vector production systems
WO2003014318A2 (fr) * 2001-08-08 2003-02-20 Genzyme Corporation Procede pour traiter le diabete et d'autres troubles lies a la glycemie
US20040143104A1 (en) * 2001-08-08 2004-07-22 Wadsworth Samuel C. Methods of treating diabetes and other blood sugar disorders
AU2002330022B2 (en) * 2001-09-13 2007-07-12 California Institute Of Technology Method for producing transgenic birds and fish
EP1438399A4 (fr) * 2001-09-28 2005-09-14 Univ North Carolina Paramyxovirus utilises comme vecteurs de transfert genique vers des cellules pulmonaires
KR20040054699A (ko) * 2001-10-02 2004-06-25 엥스띠뛰 끌레이톤 드 라 러쉐르쉬 제한된 발현의 렌티바이러스 벡터 및 이의 적용과 관련된방법 및 조성물
US7384738B2 (en) * 2002-03-28 2008-06-10 Bremel Robert D Retrovirus-based genomic screening
US20040038304A1 (en) * 2002-03-28 2004-02-26 Gala Design, Inc. Antibody libraries
ATE517122T1 (de) 2002-04-09 2011-08-15 Sanofi Pasteur Ltd Modifizierte cea-nukleinsäure und entsprechende expressionsvektoren
KR101002955B1 (ko) 2002-04-26 2010-12-21 인스티튜트 클레이톤 드 라 리쎄르셰 개선된 키메라 당단백질 및 슈도타입 렌티바이러스 벡터
WO2003093417A2 (fr) 2002-05-01 2003-11-13 Cell Genesys, Inc. Particules de vecteur lentiviral resistantes a l'inactivation d'un complement
US20050214945A1 (en) * 2002-05-17 2005-09-29 Eastern Virginia Medical School Htlv-I tax induced killing of p53 null cancer cells
US20040009158A1 (en) * 2002-07-11 2004-01-15 Washington University Promotion of neovascularization using bone marrow-derived endothelial-progenitor cells
WO2004055157A2 (fr) * 2002-08-13 2004-07-01 Whitley Chester B Procedes d'utilisation de vecteurs pour traiter des troubles metaboliques
US20060099170A1 (en) * 2002-09-13 2006-05-11 Redfield Robert R Compositions for inducing increased levels of beta-chemokines and methods of use therefor
EP1563069B1 (fr) * 2002-11-22 2012-06-06 Institut Clayton De La Recherche Compositions et systemes destines a la regulation genique
US20040197312A1 (en) 2003-04-02 2004-10-07 Marina Moskalenko Cytokine-expressing cellular vaccine combinations
WO2005001027A2 (fr) 2003-05-16 2005-01-06 University Of Maryland Biotechnology Institute Compositions de regulation de l'insensibilisation de la cellule au facteur de l'expression ccr5 et leurs methodes d'utilisation
US20050036988A1 (en) * 2003-05-28 2005-02-17 Ruian Xu Compositions and methods for preventing and treating liver cirrhosis
US7696322B2 (en) * 2003-07-28 2010-04-13 Catalent Pharma Solutions, Inc. Fusion antibodies
JP2007505130A (ja) * 2003-09-09 2007-03-08 バイレクシス コーポレイション ヒトにおいてｈｉｖに対する免疫応答を生成するための、レンチウイルスベクターベースのアプローチ
JP4668919B2 (ja) * 2003-10-08 2011-04-13 サノフィ パストゥール インコーポレイテッド 修飾ｃｅａ／ｂ７ベクター
US20050107318A1 (en) * 2003-11-17 2005-05-19 Samuel Wadsworth Methods of treating diabetes and other blood sugar disorders
EP1697534B1 (fr) 2003-12-01 2010-06-02 Life Technologies Corporation Molecule d'acide nucleique contenant des sites de recombinaison et leurs procedes d'utilisation
US20050221429A1 (en) * 2004-01-16 2005-10-06 Cardinal Health Pts, Llc Host cells containing multiple integrating vectors comprising an amplifiable marker
ATE418346T1 (de) * 2004-04-08 2009-01-15 Sangamo Biosciences Inc Zusammensetzungen zur behandlung von neuropathischen und neurodegenerativen erkrankungen
ES2527528T3 (es) * 2004-04-08 2015-01-26 Sangamo Biosciences, Inc. Métodos y composiciones para modular la contractilidad cardiaca
US20090221440A1 (en) * 2004-07-12 2009-09-03 Board Of Regents, The University Of Texas System Methods and compositions related to identifying protein-protein interactions
EP1804835B9 (fr) 2004-09-13 2010-09-29 Genzyme Corporation Constructions multimeriques
EP1858332A4 (fr) 2005-02-16 2011-06-22 Lentigen Corp Vecteurs lentiviraux et leurs utilisations
EA037929B1 (ru) 2005-03-23 2021-06-08 Генмаб А/С Антитела к cd38 человека и их применение
AR059089A1 (es) 2006-01-20 2008-03-12 Genzyme Corp Administracion intraventricular de una enzima para enfermedades de almacenamiento lisosomal
CA2641359C (fr) 2006-02-09 2022-10-04 Genzyme Corporation Administration intraventriculaire lente
EP1835032A1 (fr) 2006-03-14 2007-09-19 Université de Liège Vecteurs lentiviraux a auto-inactivation pour inhiber l'infection par VIH
US20070231298A1 (en) * 2006-03-31 2007-10-04 Cell Genesys, Inc. Cytokine-expressing cancer immunotherapy combinations
JP5623740B2 (ja) 2006-07-25 2014-11-12 セラドン・コーポレーション 遺伝子治療用アデノ随伴ウイルスベクターの長期順行性の心外膜冠動脈注入
WO2008014484A1 (fr) 2006-07-27 2008-01-31 University Of Maryland, Baltimore Récepteur cellulaire du facteur antiprolifération
WO2008066658A2 (fr) 2006-11-03 2008-06-05 The Trustees Of Princeton University Production de voies cellulaires pour une autorégulation programmée de la différentiation
US20100092435A1 (en) 2006-12-07 2010-04-15 Emmanuel Jacques Henri Joseph Wiertz Use of a varicellovirus tap-inhibitor for the induction of tumor-or virus-specific immunity against teipp
US20100291042A1 (en) 2007-05-03 2010-11-18 The Brigham And Women's Hospital, Inc. Multipotent stem cells and uses thereof
WO2008154351A1 (fr) 2007-06-06 2008-12-18 Research Development Foundation Variants du rtef-1 et leur utilisation pour inhiber l'angiogenèse
US20090028857A1 (en) * 2007-07-23 2009-01-29 Cell Genesys, Inc. Pd-1 antibodies in combination with a cytokine-secreting cell and methods of use thereof
US8425897B2 (en) * 2007-08-30 2013-04-23 Immutep S.A. Compositions containing LAG-3 and cells that secrete GM-CSF and methods of use
CA2703045C (fr) * 2007-10-25 2017-02-14 Sangamo Biosciences, Inc. Procedes et compositions pour une integration ciblee
DK2222697T3 (da) 2007-11-01 2013-03-11 Perseid Therapeutics Llc Immunsuppressive polypeptider og nukleinsyrer
MX2010007530A (es) 2008-01-10 2010-11-10 Res Dev Foundation Vacunas y diagnosticos para ehrlichiosis.
US9746471B2 (en) 2008-01-25 2017-08-29 Multivir Inc. P53 biomarkers
KR100981092B1 (ko) 2008-02-29 2010-09-08 고려대학교 산학협력단 제8 혈액응고 인자와 폰 빌리 블란트 인자 변이체의 재조합발현 벡터 시스템
WO2009117439A2 (fr) 2008-03-17 2009-09-24 The Scripps Research Institute Approches chimiques et génétiques combinées pour la génération de cellules souches pluripotentes induites
CA2719938A1 (fr) * 2008-03-28 2009-10-01 Virxsys Corporation Vecteurs immunogenes a base de lentivirus
CA2721870C (fr) 2008-04-21 2020-12-22 Tissue Regeneration Therapeutics, Inc. Cellules perivasculaires genetiquement modifiees de cordon ombilical humain pour une prophylaxie ou un traitement d'agents biologiques ou chimiques
CA2734128A1 (fr) 2008-08-12 2010-02-18 Cellular Dynamics International, Inc. Procedes de production de cellules ips
WO2010022089A2 (fr) 2008-08-18 2010-02-25 University Of Maryland, Baltimore Dérivés d’apf et méthodes d’utilisation afférentes
US8840881B2 (en) 2008-08-28 2014-09-23 Aduro Gvax Inc. Methods and compositions for treating prostate cancer or inducing a humoral immune response against prostate cancer
SG172160A1 (en) 2008-12-17 2011-07-28 Scripps Research Inst Generation and maintenance of stem cells
WO2010087702A1 (fr) 2009-01-30 2010-08-05 Stichting Katholieke Universiteit Gène tet2 en tant que marqueur pour diagnostiquer un syndrome myélodysplasique (mds) ou une leucémie myéloïde aiguë (aml) et déterminer le pronostic chez un sujet
PL2393917T3 (pl) 2009-02-03 2016-12-30 Podłoże do hodowli nabłonkowych komórek macierzystych i organoidów zawierających komórki macierzyste
US9752124B2 (en) 2009-02-03 2017-09-05 Koninklijke Nederlandse Akademie Van Wetenschappen Culture medium for epithelial stem cells and organoids comprising the stem cells
EP2412800A1 (fr) 2010-07-29 2012-02-01 Koninklijke Nederlandse Akademie van Wetenschappen Organoïde du foie, ses utilisations et son procédé de culture pour l'obtenir
WO2010105251A2 (fr) * 2009-03-13 2010-09-16 Lentigen Corporation Vaccins à vecteurs rétroviraux non intégrants
EP2419511B1 (fr) 2009-04-09 2018-01-17 Sangamo Therapeutics, Inc. Intégration ciblée dans des cellules souches
EP2424885B1 (fr) 2009-04-28 2016-03-23 Vanderbilt University Compositions et procédés pour le traitement de troubles mettant en jeu une apoptose de cellules épithéliales
KR101756354B1 (ko) 2009-07-31 2017-07-26 백스터 인터내셔널 인코포레이티드 Ａｄａｍｔｓ 단백질 발현을 위한 세포 배양 배지
EP2478101A1 (fr) 2009-09-16 2012-07-25 Stichting Het Nederlands Kanker Instituut Gènes cibles fra-1 utilisés comme cibles médicamenteuses pour le traitement du cancer
MX339205B (es) 2009-09-21 2016-05-16 Baxalta Inc Formulaciones de adamts13 liquidas y liofilizadas, estabilizadas.
EP2305717A1 (fr) 2009-09-21 2011-04-06 Koninklijke Nederlandse Akademie van Wetenschappen Inhibition du TNIK pour le traitement du cancer du côlon
MX337982B (es) 2009-10-16 2016-03-30 Scripps Research Inst Induccion de celulas pluripotentes.
WO2011100058A1 (fr) 2010-02-09 2011-08-18 Sangamo Biosciences, Inc. Modification génomique ciblée avec des molécules donneuses partiellement monocaténaires
US10787701B2 (en) 2010-04-05 2020-09-29 Prognosys Biosciences, Inc. Spatially encoded biological assays
CA2796601C (fr) 2010-04-19 2019-03-26 Research Development Foundation Variants de rtef-1 et utilisations de ceux-ci
CA2801913C (fr) * 2010-05-27 2019-01-22 HEINRICH-PETTE-INSTITUT LEIBNIZ-INSTITUT FUR EXPERIMENTELLE VIROLOGIE - - stiftung buergerlichen rechts Recombinase mise au point sur mesure pour recombiner des sites asymetriques voulus dans une pluralite de souches de retrovirus
CA2802087A1 (fr) 2010-06-15 2011-12-22 Cellular Dynamics International, Inc. Compendium de modeles de cellules souches prefabriques pour l'interrogation d'une reponse biologique
US8785192B2 (en) 2010-07-07 2014-07-22 Cellular Dynamics International, Inc. Endothelial cell production by programming
PL2590998T3 (pl) 2010-07-08 2018-05-30 Baxalta GmbH SPOSÓB WYTWARZANIA REKOMBINOWANEGO vWF O DUŻEJ MASIE CZĄSTECZKOWEJ W HODOWLI KOMÓRKOWEJ
US9309534B2 (en) 2010-07-12 2016-04-12 Universidad Autonoma De Barcelona Gene therapy composition for use in diabetes treatment
US20120083035A1 (en) * 2010-09-30 2012-04-05 Dharmacon, Inc. Modified Cell Lines for Increasing Lentiviral Titers
WO2012047093A1 (fr) 2010-10-05 2012-04-12 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Traitement du syndrome de sjögren
EP2465928A1 (fr) 2010-12-16 2012-06-20 Academisch Medisch Centrum bij de Universiteit van Amsterdam Traitement des maladies liées au Th17
KR101975688B1 (ko) 2010-12-22 2019-05-07 페이트 세러퓨틱스, 인코포레이티드 단세포 분류 및 iPSC의 증강된 재프로그래밍을 위한 세포 배양 플랫폼
BRPI1105317A2 (pt) 2011-01-24 2013-04-30 Fundacco Hemoct De Ribeirco Preto produÇço estÁvel e em larga escala de fviii humano em linhagem celular humana sk-hep-1
EP2673358B1 (fr) 2011-02-08 2019-01-09 FUJIFILM Cellular Dynamics, Inc. Production de précurseurs hématopoïétiques obtenus par programmation
EP2741784B1 (fr) 2011-03-02 2017-05-17 Board Of Regents, The University Of Texas System Therapies de tusc2
ES2931180T3 (es) 2011-05-19 2022-12-27 Fund Publica Andaluza Progreso Y Salud Sistema de tipo Tet-on lentivírico de promotor dual muy inducible
WO2012170911A2 (fr) 2011-06-10 2012-12-13 Bluebird Bio, Inc. Vecteurs de thérapie génique pour l'adrénoleucodystrophie et l'adrénomyéloneuropathie
EP2732029B1 (fr) 2011-07-11 2019-01-16 FUJIFILM Cellular Dynamics, Inc. Procédés de reprogrammation cellulaire et d'ingénierie génomique
WO2013026015A1 (fr) 2011-08-18 2013-02-21 Dana-Farber Cancer Institute, Inc. Pièges de ligand de muc1 pour l'utilisation dans le traitement de cancers
WO2013043196A1 (fr) 2011-09-23 2013-03-28 Bluebird Bio, Inc. Procédés de thérapie génique améliorés
SG10201602423TA (en) 2011-09-30 2016-05-30 Bluebird Bio Inc Compounds For Improved Viral Transduction
MX354516B (es) 2011-10-27 2018-03-08 Wellstat Ophthalmics Corp Vectores que codifican el factor de viabilidad de conos derivado de bastones.
GB201202516D0 (en) 2012-02-13 2012-03-28 Ucl Business Plc Materials and methods relating to packaging cell lines
TWI775096B (zh) 2012-05-15 2022-08-21 澳大利亞商艾佛蘭屈澳洲私營有限公司 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd)
JP6445971B2 (ja) 2012-05-30 2018-12-26 コーネル ユニヴァーシティー ヒト羊水由来細胞からの機能的かつ耐久性のある内皮細胞の生成
AU2013281328B2 (en) 2012-06-27 2017-11-23 Meiragtx Uk Ii Limited Combination for treating an inflammatory disorder
UA114108C2 (uk) 2012-07-10 2017-04-25 Борд Оф Ріджентс, Дзе Юніверсіті Оф Техас Сістем Моноклональне антитіло для застосування в діагностиці і терапії злоякісних пухлин і аутоімунного захворювання
PT2852668T (pt) 2012-07-12 2016-07-13 Proqr Therapeutics Ii Bv Oligonucleótidos para fazer uma alteração na sequência de uma molécula de rna alvo presente numa célula viva
WO2014022455A1 (fr) 2012-07-31 2014-02-06 The Board Of Regents Of The University Of Texas System Procédés et compositions pour l'induction in vivo de la formation de cellules bêta pancréatiques
EP2692868A1 (fr) 2012-08-02 2014-02-05 Universitat Autònoma De Barcelona Vecteurs viraux adéno-associés (AAV) utiles pour la transduction de tissu adipeux
JP2015529466A (ja) * 2012-09-14 2015-10-08 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 鎌状赤血球症の幹細胞遺伝子治療のためのレンチウイルスベクター
EP3511423B2 (fr) 2012-10-17 2024-05-29 Spatial Transcriptomics AB Procédés et produits pour optimiser la detection localisée ou spatiale de l'expression génique dans un échantillon de tissu
AU2013204922B2 (en) 2012-12-20 2015-05-14 Celgene Corporation Chimeric antigen receptors
AU2014214850C1 (en) 2013-02-06 2018-12-06 Celgene Corporation Modified T lymphocytes having improved specificity
AU2014218807A1 (en) 2013-02-22 2015-09-03 Cellular Dynamics International, Inc. Hepatocyte production via forward programming by combined genetic and chemical engineering
US20160010094A1 (en) 2013-03-01 2016-01-14 University Of Pretoria Transgenic cell selection
CA2904236A1 (fr) 2013-03-05 2014-09-12 Baylor College Of Medicine Expression de l'heparanase dans des lymphocytes t humains
CA2904230A1 (fr) 2013-03-05 2014-09-12 Baylor College Of Medicine Cellules d'engagement pour immunotherapie
AU2014225365B2 (en) 2013-03-07 2019-09-12 Baylor College Of Medicine Targeting CD138 in cancer
EP2964764A1 (fr) 2013-03-09 2016-01-13 Baylor College Of Medicine Traitement par lymphocytes t à ciblage vasculaire
AU2013202965B2 (en) 2013-03-15 2016-07-21 Takeda Pharmaceutical Company Limited Improved method for producing factor h from a plasma precipitation fraction
TW201522637A (zh) 2013-03-15 2015-06-16 Jackson Lab 非胚胎幹細胞之單離及其用途
EP2970920B1 (fr) 2013-03-15 2018-04-25 The Children's Hospital of Philadelphia Procédé de fabrication pouvant être mis à l'échelle pour produire des vecteurs lentiviraux recombinants dans un système de culture cellulaire en suspension sans sérum
CA2907397C (fr) 2013-03-15 2022-11-22 Anthrogenesis Corporation Lymphocytes t modifies
CA2908668C (fr) 2013-04-03 2023-03-14 Memorial Sloan-Kettering Cancer Center Generation efficace de lymphocytes t ciblant une tumeur derives de cellules souches pluripotentes
US9868979B2 (en) 2013-06-25 2018-01-16 Prognosys Biosciences, Inc. Spatially encoded biological assays using a microfluidic device
CA2923857A1 (fr) 2013-09-09 2015-03-12 Figene, Llc Therapie genique pour la regeneration de cellules de type chondrocytes ou cartilagineuses
CN105705140A (zh) 2013-11-05 2016-06-22 克隆技术实验室有限公司 干转染组合物及其制备和使用方法
EP3065775B1 (fr) 2013-11-08 2020-09-30 The Board of Regents of the University of Texas System Anticorps vh4 dirigés contre les astrocytes et les neurones de la matière grise
CA2929555A1 (fr) 2013-11-08 2015-05-14 Baylor Research Institute La localisation nucleaire de glp-1 stimule la regeneration myocardique et entraine la regression d'une insuffisance cardiaque
US10801070B2 (en) 2013-11-25 2020-10-13 The Broad Institute, Inc. Compositions and methods for diagnosing, evaluating and treating cancer
EP3074025A1 (fr) 2013-11-27 2016-10-05 Baylor College Of Medicine Récepteur antigénique chimère spécifique de cspg4 utilisable contre le cancer
US11725237B2 (en) 2013-12-05 2023-08-15 The Broad Institute Inc. Polymorphic gene typing and somatic change detection using sequencing data
GB201322626D0 (en) 2013-12-19 2014-02-05 Immutep S A Combined preparations for the treatment of cancer
BR112016014410A2 (pt) 2013-12-20 2018-02-20 The Broad Institute Inc. terapia de combinação com vacina de neoantígeno
JP6908381B2 (ja) 2014-01-29 2021-07-28 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド Ｍｕｃ１−ｃ／細胞外ドメイン（ｍｕｃ１−ｃ／ｅｃｄ）に対する抗体
EP3110836A1 (fr) 2014-02-25 2017-01-04 Research Development Foundation Peptides sty pour l'inhibition de l'angiogenèse
SG11201606934SA (en) 2014-03-04 2016-09-29 Fate Therapeutics Inc Improved reprogramming methods and cell culture platforms
CN106414474B (zh) 2014-03-17 2021-01-15 阿德夫拉姆生物技术股份有限公司 用于视锥细胞中增强的基因表达的组合物和方法
US20170107486A1 (en) 2014-04-21 2017-04-20 Cellular Dynamics International, Inc. Hepatocyte production via forward programming by combined genetic and chemical engineering
SG11201608744VA (en) 2014-04-25 2016-11-29 Bluebird Bio Inc Improved methods for manufacturing adoptive cell therapies
CA2946585C (fr) 2014-04-25 2023-09-19 Bluebird Bio, Inc. Recepteurs d'antigenes chimeriques de promoteur mnd
HUE053101T2 (hu) 2014-06-06 2021-06-28 Bluebird Bio Inc Javított T-sejt-készítmények
EP2957634A1 (fr) 2014-06-20 2015-12-23 Consejo Superior De Investigaciones Científicas Composés pour la prévention et/ou le traitement de maladies fibrotiques
JP6754761B2 (ja) 2014-07-11 2020-09-16 セルジーン コーポレイション Ｔリンパ球へのベクター導入効率の改善方法
US20170226216A1 (en) 2014-07-24 2017-08-10 Bluebird Bio, Inc. Bcma chimeric antigen receptors
EP2977463A1 (fr) 2014-07-25 2016-01-27 Centro de Investigación Biomédica en Red (CIBER) Procédés et agents associés à des maladies pulmonaires
SG11201700724PA (en) 2014-07-31 2017-02-27 Univ Oklahoma High isomerohydrolase activity mutants of mammalian rpe65
SG11201701111SA (en) 2014-08-12 2017-03-30 Anthrogenesis Corp Car-t lymphocytes engineered to home to lymph node b cell zone, skin, or gastrointestinal tract
WO2016025510A1 (fr) 2014-08-12 2016-02-18 Rappolee Daniel A Systèmes et méthodes de détection du stress dans les cellules souches et leurs utilisations
US11111288B2 (en) 2014-08-28 2021-09-07 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified t-cells
WO2016030501A1 (fr) 2014-08-28 2016-03-03 Centre National De La Recherche Scientifique - Cnrs - Vecteurs synthétiques de rétrotransposon alu destinés à la thérapie génique
AU2015308818B2 (en) 2014-08-28 2021-02-25 Bioatla Llc Conditionally active chimeric antigen receptors for modified T-cells
AU2015311911B2 (en) 2014-09-03 2019-01-24 Bioatla, Llc Discovering and producing conditionally active biologic proteins in the same eukaryotic cell production hosts
LT3194602T (lt) 2014-09-18 2020-05-11 Université de Montréal Junginiai ir būdai, skirti virusinių genų pernešimui į žmogaus hematopoetines ląsteles
US20170281683A1 (en) 2014-09-26 2017-10-05 Baylor College Of Medicine Glypican-3 specific chimeric antigen receptors for adoptive immunotherapy
LT3628687T (lt) 2014-12-12 2021-11-10 2Seventy Bio, Inc. Chimeriniai bcma antigeno receptoriai
IL302660A (en) 2014-12-19 2023-07-01 Dana Farber Cancer Inst Inc Chimeric antigen receptors and methods of use thereof
US10870705B2 (en) 2014-12-19 2020-12-22 Dana-Farber Cancer Institute, Inc. Chimeric antigen receptors specific for carbonic acid anhydrase IX
EP3234130B1 (fr) 2014-12-19 2020-11-25 The Broad Institute, Inc. Procédé pour profiler le répertoire de récepteurs de cellulles t.
EP3234193B1 (fr) 2014-12-19 2020-07-15 Massachusetts Institute of Technology Biomarqueurs moléculaires pour l'immunothérapie d'un cancer
EP3242945B1 (fr) 2015-01-07 2021-09-01 Universitat Autònoma de Barcelona Construction génique à vecteur unique comprenant des gènes de l'insuline et de la glucokinase
GB201500374D0 (en) 2015-01-09 2015-02-25 Immutep S A Combined preparations for the treatment of cancer
MA41346A (fr) 2015-01-12 2017-11-21 Juno Therapeutics Inc Eléments régulateurs post-transcriptionnels d'hépatite modifiée
MA41433A (fr) 2015-01-26 2017-12-05 Baylor College Medicine Cellules immunitaires universelles pour l'immunothérapie anticancéreuse
CN114133450B (zh) 2015-02-03 2023-09-22 国家健康与医学研究院 抗-Rho GTPase的构象单域抗体及其用途
WO2016134293A1 (fr) 2015-02-20 2016-08-25 Baylor College Of Medicine Inactivation de p63 pour le traitement de l'insuffisance cardiaque
JP7095994B2 (ja) 2015-03-02 2022-07-05 アドヴェラム バイオテクノロジーズ， インコーポレイテッド ポリヌクレオチドを網膜錐体に硝子体内送達するための組成物及び方法
US20180271891A1 (en) 2015-03-11 2018-09-27 The Broad Institute Inc. Selective treatment of prmt5 dependent cancer
WO2016172606A1 (fr) 2015-04-23 2016-10-27 Baylor College Of Medicine Récepteur antigénique chimérique ciblant le cd5 pour une thérapie adoptive à base de cellules t
IL294183B2 (en) 2015-05-20 2023-10-01 Dana Farber Cancer Inst Inc Shared neoantigens
WO2016185026A1 (fr) 2015-05-20 2016-11-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Procédés et composition pharmaceutique pour la modulation de la polarisation et de l'activation des macrophages
TWI750122B (zh) 2015-06-09 2021-12-21 美商博德研究所有限公司 用於贅瘤疫苗之調配物及其製備方法
US11040094B2 (en) 2015-07-01 2021-06-22 Colleen M. O'Connor Compositions and methods for treating immunological dysfunction
EP4043074A1 (fr) 2015-08-14 2022-08-17 The University of Sydney Inhibition de la connexine 45 pour la thérapie
AU2016315704B2 (en) 2015-08-31 2022-08-11 Helixmith Co., Ltd Anti-sialyl Tn chimeric antigen receptors
WO2017055248A1 (fr) 2015-09-28 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Méthodes et compositions pharmaceutiques pour le traitement d'une insuffisance cardiaque
SG10202111851YA (en) 2015-10-16 2021-12-30 Fate Therapeutics Inc Platform for the Induction & Maintenance of Ground State Pluripotency
KR20180063333A (ko) 2015-10-20 2018-06-11 후지필름 셀룰러 다이내믹스, 인코포레이티드 면역 세포로의 만능 줄기 세포의 지정된 분화 방법
CN116875635A (zh) 2015-10-22 2023-10-13 朱诺治疗学有限公司 用于转导的方法、反应剂盒、反应剂和设备
KR102669457B1 (ko) 2015-10-23 2024-05-24 더 잭슨 래보라토리 안구 신경변성 장애(예, 녹내장)의 치료 및 예방에 사용되는 니코틴아미드
CA3003144A1 (fr) 2015-10-30 2017-05-04 Aleta Biotherapeutics Inc. Compositions et methodes de transduction tumorale
EP3368559A4 (fr) 2015-10-30 2020-01-15 Aleta Biotherapeutics Inc. Compositions et méthodes pour le du traitement du cancer
LT3370733T (lt) 2015-11-02 2021-10-25 Board Of Regents, The University Of Texas System Cd40 aktyvinimo ir imuninės kontrolės taškų blokados būdai
US20190038713A1 (en) 2015-11-07 2019-02-07 Multivir Inc. Compositions comprising tumor suppressor gene therapy and immune checkpoint blockade for the treatment of cancer
SG11201804070XA (en) 2015-11-13 2018-06-28 Baxalta Inc Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a
CA3005565A1 (fr) 2015-11-13 2017-05-18 Baxalta Incorporated Vecteurs viraux codant pour des variants du facteur viii de recombinaison avec une expression augmentee pour la therapie genique de l'hemophilie a
US11479755B2 (en) 2015-12-07 2022-10-25 2Seventy Bio, Inc. T cell compositions
GB2545763A (en) 2015-12-23 2017-06-28 Adverum Biotechnologies Inc Mutant viral capsid libraries and related systems and methods
EP3413896B1 (fr) 2016-02-12 2021-03-17 Bluebird Bio, Inc. Compositions d'augmentation de vcn et ses procédés d'utilisation
KR20180110112A (ko) 2016-02-12 2018-10-08 블루버드 바이오, 인코포레이티드. Vcn 인핸서 조성물 및 이의 사용 방법
WO2017143076A1 (fr) 2016-02-16 2017-08-24 Dana-Farber Cancer Institute, Inc. Récepteurs antigéniques chimériques et leurs procédés d'utilisation
WO2017143094A1 (fr) 2016-02-16 2017-08-24 Dana-Farber Cancer Institute, Inc. Compositions d'immunothérapie et méthodes associées
US10435682B2 (en) 2016-02-19 2019-10-08 University Of South Florida Arginine deiminase gene therapy for disordered proteins
WO2017168348A1 (fr) 2016-03-31 2017-10-05 Baylor Research Institute Protéine 8 de type angiopoïétine (angptl8)
AU2017250773A1 (en) 2016-04-14 2018-11-08 2Seventy Bio, Inc. Salvage chimeric antigen receptor systems
WO2017184590A1 (fr) 2016-04-18 2017-10-26 The Broad Institute Inc. Prédiction améliorée d'épitope hla
PL3445406T3 (pl) 2016-04-20 2022-02-07 Centro De Investigaciones Energéticas, Medioambientales Y Tecnológicas, O.A., M.P. Kompozycje i sposoby zwiększonej ekspresji genów PKLR
US20190125826A1 (en) 2016-04-22 2019-05-02 Inserm (Institut National De La Santé Et De La Médicale) Methods and pharmaceutical composition for the treatment of inflammatory skin diseases associated with desmoglein-1 deficiency
MX394735B (es) 2016-05-13 2025-03-24 Bioatla Llc Anticuerpos anti-ror2, fragmentos de anticuerpos, sus inmunoconjugados y usos de los mismos.
CN109997041B (zh) 2016-06-10 2022-10-28 歌德塔有限公司 人白细胞抗原限制的γδT细胞受体及其使用方法
WO2018005975A1 (fr) 2016-07-01 2018-01-04 Research Development Foundation Élimination de cellules proliférantes de greffons dérivés de cellules souches
ES2926513T3 (es) 2016-07-29 2022-10-26 Juno Therapeutics Inc Métodos para evaluar la presencia o ausencia de virus competente en replicación
US11866733B2 (en) 2016-08-01 2024-01-09 University of Pittsburgh—of the Commonwealth System of Higher Education Human induced pluripotent stem cells for high efficiency genetic engineering
MA45996A (fr) 2016-08-16 2021-06-02 Bluebird Bio Inc Variants d'endonucléase de homing du récepteur alpha de l'il-10, compositions et méthodes d'utilisation associées
EP3504335A4 (fr) 2016-08-23 2020-04-15 Bluebird Bio, Inc. Variants de l'endonucléase homing tim3, compositions et procédés d'utilisation
US12102652B2 (en) 2016-08-26 2024-10-01 Baylor College Of Medicine Constitutively active cytokine receptors for cell therapy
MX2019002725A (es) 2016-09-08 2019-05-27 Bluebird Bio Inc Variantes de endonucleasas de asentamiento pd-1, composiciones y metodos de uso.
DK3757120T3 (da) 2016-10-04 2022-07-25 Prec Biosciences Inc Co-stimulerende domæner til anvendelse i genetisk modificerede celler
EP3523422B1 (fr) 2016-10-05 2024-12-25 FUJIFILM Cellular Dynamics, Inc. Génération de lignées matures à partir de cellules souches pluripotentes induites avec une interruption mecp2
US11052131B2 (en) 2016-10-05 2021-07-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of kidney cancer
US20200263139A1 (en) 2016-10-05 2020-08-20 FUJIFILM Cellular Dynamics, Inc. Methods for directed differentiation of pluripotent stem cells to hla homozygous immune cells
WO2018069422A1 (fr) 2016-10-12 2018-04-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Procédés et compositions pharmaceutiques destinés au traitement de la stéatohépatite non alcoolique
MX386249B (es) 2016-10-12 2025-03-18 Univ Texas Terapia tusc2 para usarse en el tratamiento de cáncer.
CA3040157A1 (fr) 2016-10-17 2018-04-26 Bluebird Bio, Inc. Variants de l'endonuclease tgf.beta.r2, compositions et procedes d'utilisation
JP7100028B2 (ja) 2016-10-20 2022-07-12 セルジーン コーポレイション セレブロン系のヘテロ二量体化可能なキメラ抗原受容体
US12109234B2 (en) 2016-11-04 2024-10-08 2Seventy Bio, Inc. Anti-BCMA CAR T cell compositions
IL266628B2 (en) 2016-11-17 2024-06-01 Bluebird Bio Inc TGFBeta SIGNAL CONVERTOR
EP3541830A1 (fr) 2016-11-17 2019-09-25 INSERM (Institut National de la Santé et de la Recherche Médicale) Procédés et compositions pharmaceutiques pour augmenter le niveau de protéine endogène
KR20190098747A (ko) 2016-12-05 2019-08-22 주노 쎄러퓨티크스 인코퍼레이티드 입양 세포 치료법을 위한 조작된 세포의 제조방법
EP3548617A4 (fr) 2016-12-05 2020-06-17 The Regents of The University of California Vecteur lentiviral optimisé pour une thérapie par cellules souches d'hémoglobinopathies
US20200009203A1 (en) 2016-12-12 2020-01-09 Multivir Inc. Methods and compositions comprising viral gene therapy and an immune checkpoint inhibitor for treatment and prevention of cancer and infectious diseases
WO2018130518A1 (fr) 2017-01-10 2018-07-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Procédés et composition pharmaceutique d'induction de la sénescence dans des cellules cancéreuses
US11549149B2 (en) 2017-01-24 2023-01-10 The Broad Institute, Inc. Compositions and methods for detecting a mutant variant of a polynucleotide
US20190367944A1 (en) 2017-01-30 2019-12-05 The U.S.A., As Represented By The Secretary, Department Of Health And Human Services Recombinant virus vectors for the treatment of glycogen storage disease
FI3580561T3 (fi) 2017-02-12 2023-12-12 Biontech Us Inc Hla-pohjaiset menetelmät ja koostumukset sekä niiden käyttö
EP3583201B1 (fr) 2017-02-14 2024-01-17 University of Pittsburgh - Of the Commonwealth System of Higher Education Procédés d'ingénierie de cellules souches pluripotentes induites humaines pour produire un tissu hépatique
CA3053499A1 (fr) 2017-02-15 2018-08-23 Bluebird Bio, Inc. Modeles de reparation de donneur pour l'edition de genome multiplex
WO2018175476A1 (fr) 2017-03-20 2018-09-27 Baylor College Of Medicine C-mpl transgénique pour introduire des signaux de co-stimulation et cytokine ligand-dépendants dans des cellules génétiquement modifiées par tcr
WO2018183293A1 (fr) 2017-03-28 2018-10-04 The Trustees Of The University Of Pennsylvania Méthodes de protection de tissu greffé contre le rejet
EP3388520A1 (fr) 2017-04-11 2018-10-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Procédés et composition pharmaceutique pour réduire l'expression de nkcc1 chez un sujet en ayant besoin
MX2019011897A (es) 2017-04-18 2019-11-28 Fujifilm Cellular Dynamics Inc Celulas efectoras inmunitarias especificas de antigenos.
US20210139932A1 (en) 2017-05-03 2021-05-13 Biomarin Pharmaceutical Inc. Improved lentiviruses for transduction of hematopoietic stem cells
EP3634493A1 (fr) 2017-05-08 2020-04-15 Precision BioSciences, Inc. Molécules d'acide nucléique codant pour un récepteur d'antigène modifié et molécule d'acide nucléique inhibitrice et leurs méthodes d'utilisation
EP3624823A1 (fr) 2017-05-18 2020-03-25 UMC Utrecht Holding B.V. Compositions et procédés pour thérapies de ciblage de cellules
EP3630974A1 (fr) 2017-05-22 2020-04-08 Baxalta Incorporated Vecteurs viraux codant pour des fix de recombinaison avec une expression accrue pour la thérapie génique de l'hémophilie b
AU2018274655B2 (en) 2017-05-24 2025-01-30 Universitat Autonoma De Barcelona Viral expression construct comprising a fibroblast growth factor 21 (FGF21) coding sequence
CN110799644A (zh) 2017-05-25 2020-02-14 蓝鸟生物公司 Cblb核酸内切酶变体、组合物及使用方法
JP2020529834A (ja) 2017-06-30 2020-10-15 プレシジョン バイオサイエンシズ，インク． Ｔ細胞受容体アルファ遺伝子の改変されたイントロンを含む遺伝子改変ｔ細胞
US20210228738A1 (en) 2017-07-17 2021-07-29 INSERM (Institut National de la Santé et de la Recherche Médicale) Compositions and methods for increasing or enhancing transduction of gene therapy vectors and for removing or reducing immunoglobulins
US20230242654A1 (en) 2017-07-29 2023-08-03 Juno Therapeutics, Inc. Reagents for expanding cells expressing recombinant receptors
KR102793810B1 (ko) * 2017-08-04 2025-04-11 가톨릭대학교 산학협력단 간세포성장인자를 발현하는 중간엽줄기세포를 유효성분으로 포함하는 혈관계 질환 예방 또는 치료용 약학적 조성물
MX2020001490A (es) 2017-08-09 2020-08-06 Juno Therapeutics Inc Metodos para producir composiciones de celulas geneticamente modificadas y composiciones relacionadas.
WO2019057742A1 (fr) 2017-09-20 2019-03-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Méthodes et compositions pharmaceutiques pour la modulation de l'autophagie
US11579147B2 (en) 2017-09-25 2023-02-14 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of VNN1 as a biomarker and a therapeutic target in sarcomas
EP4269560A3 (fr) 2017-10-03 2024-01-17 Precision Biosciences, Inc. Peptides de récepteur de facteur de croissance épidermique modifiés destinés à être utilisés dans des cellules génétiquement modifiées
US11779654B2 (en) 2017-10-04 2023-10-10 2Seventy Bio, Inc. PCSK9 endonuclease variants, compositions, and methods of use
SG11202003657VA (en) 2017-11-01 2020-05-28 Juno Therapeutics Inc Process for producing a t cell composition
MA50855A (fr) 2017-11-01 2020-09-09 Juno Therapeutics Inc Procédé de génération de compositions thérapeutiques de cellules modifiées
KR20200095487A (ko) 2017-11-10 2020-08-10 주노 쎄러퓨티크스 인코퍼레이티드 폐쇄-시스템 극저온 용기
MX2020005907A (es) 2017-12-08 2020-10-19 Juno Therapeutics Inc Formulacion de medio libre de suero para cultivar celulas y metodos de uso de la misma.
CA3084446A1 (fr) 2017-12-08 2019-06-13 Juno Therapeutics, Inc. Marqueurs phenotypiques pour therapie cellulaire et procedes associes
JP7416716B2 (ja) 2017-12-28 2024-01-17 トラクト ファーマシューティカルズ インコーポレイテッド 円柱上皮幹細胞のための幹細胞培養系およびそれに関連した使用法
DE102018010282A1 (de) 2018-01-17 2019-07-18 Immatics US, Inc. Verfahren zur Feststellung der Wirksamkeit von viralen Vektoren
DE102018100967B4 (de) 2018-01-17 2019-08-14 Immatics US, Inc. Verfahren zur feststellung der wirksamkeit von viralen vektoren
CN111918972A (zh) 2018-01-31 2020-11-10 朱诺治疗学股份有限公司 评估存在或不存在有复制能力的病毒的方法和试剂
JP2021518104A (ja) 2018-03-14 2021-08-02 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド 操作された細胞、ｔ細胞免疫調節抗体、およびそれらの使用方法
AU2019322487B2 (en) 2018-03-19 2024-04-18 Multivir Inc. Methods and compositions comprising tumor suppressor gene therapy and CD122/CD132 agonists for the treatment of cancer
AU2019244479B2 (en) 2018-03-30 2024-12-19 Les Hopitaux Universitaires De Geneve Micro RNA expression constructs and uses thereof
AU2019252285A1 (en) 2018-04-12 2020-10-29 Umoja Biopharma, Inc. Viral vectors and packaging cell lines
KR20210021473A (ko) 2018-05-15 2021-02-26 플래그쉽 파이어니어링 이노베이션스 브이, 인크. 푸소솜 조성물 및 그의 용도
WO2019219979A1 (fr) 2018-05-18 2019-11-21 Umc Utrecht Holding B.V. Compositions et procédés pour thérapies de ciblage de cellules
EP3806888B1 (fr) 2018-06-12 2024-01-31 Obsidian Therapeutics, Inc. Constructions régulatrices dérivées de pde5 et procédés d'utilisation en immunothérapie
EP4365194A3 (fr) 2018-06-14 2024-07-24 Regeneron Pharmaceuticals, Inc. Récepteurs antigéniques chimériques anti-cd79a
WO2019238934A1 (fr) 2018-06-15 2019-12-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Utilisation de l'apolipoprotéine m pour le traitement et le diagnostic de la résistance à l'insuline
BR112021000145A2 (pt) 2018-07-09 2021-04-06 Flagship Pioneering Innovations V, Inc Composições de fusossoma e usos das mesmas
SG11202100160SA (en) 2018-07-11 2021-02-25 Celgene Corp Uses of anti-bcma chimeric antigen receptors
CA3106010A1 (fr) 2018-07-12 2020-01-16 Rocket Pharmaceuticals, Ltd. Vecteurs de therapie genique pour le traitement de la maladie de danon
JP2021530524A (ja) 2018-07-16 2021-11-11 バクスアルタ インコーポレイテッド 発現が増強された組換えｆｖｉｉｉ変異体をコードするウイルスベクターを使用する血友病ａの遺伝子療法
KR20210102870A (ko) 2018-08-30 2021-08-20 테나야 테라퓨틱스, 인코포레이티드 미오카르딘 및 ascl1을 사용한 심장 세포 재프로그래밍
SG11202102290RA (en) 2018-09-06 2021-04-29 Centre Leon Berard Herv-k-derived antigens as shared tumor antigens for anti-cancer vaccine
US20220031807A1 (en) 2018-09-27 2022-02-03 INSERM (Institut National de la Santé et de la Recherche Médicale Methods and pharmaceutical composition reducing skin inflammation
US20210382068A1 (en) 2018-10-02 2021-12-09 Dana-Farber Cancer Institute, Inc. Hla single allele lines
WO2020072059A1 (fr) 2018-10-04 2020-04-09 Bluebird Bio, Inc. Variants de l'endonucléase cblb, compositions et méthodes d'utilisation
WO2020086742A1 (fr) 2018-10-24 2020-04-30 Obsidian Therapeutics, Inc. Régulation de protéine accordable par er
CN113646335A (zh) 2018-11-01 2021-11-12 朱诺治疗学股份有限公司 使用对b细胞成熟抗原具有特异性的嵌合抗原受体的治疗的方法
AU2019378881A1 (en) 2018-11-14 2021-06-03 Flagship Pioneering Innovations V, Inc. Fusosome compositions for CNS delivery
AU2019380517A1 (en) 2018-11-14 2021-06-03 Flagship Pioneering Innovations V, Inc. Fusosome compositions for hematopoietic stem cell delivery
BR112021009420A2 (pt) 2018-11-16 2021-11-23 Juno Therapeutics Inc Métodos de dosagem de células t manipuladas para o tratamento de malignidades de células b
US20220017920A1 (en) 2018-11-21 2022-01-20 Umoja Biopharma, Inc. Multicistronic vector for surface engineering lentiviral particles
WO2020109314A1 (fr) 2018-11-26 2020-06-04 Universitat Autonoma De Barcelona Thérapie génique basée sur le facteur de croissance des fibroblastes 21 (fgf21)
US20220031749A1 (en) 2018-11-28 2022-02-03 Board Of Regents, The University Of Texas System Multiplex genome editing of immune cells to enhance functionality and resistance to suppressive environment
EP3886874B1 (fr) 2018-11-29 2024-12-11 Board of Regents, The University of Texas System Procédés pour l'expansion ex vivo de cellules tueuses naturelles et utilisation associée
ES2981569T3 (es) 2018-11-30 2024-10-09 Juno Therapeutics Inc Métodos de tratamiento usando terapia celular adoptiva
BR112021010120A2 (pt) 2018-11-30 2021-08-31 Juno Therapeutics, Inc. Métodos para dosagem e tratamento de malignidades celulares em terapia celular adotiva
MX2021006241A (es) 2018-12-04 2021-08-11 Catalent Pharma Solutions Llc Vectores para la fabricacion de proteinas.
US12227551B2 (en) 2018-12-11 2025-02-18 Obsidian Therapeutics, Inc. Membrane bound IL12 compositions and methods for tunable regulation
US20220062394A1 (en) 2018-12-17 2022-03-03 The Broad Institute, Inc. Methods for identifying neoantigens
KR102670790B1 (ko) 2018-12-21 2024-05-29 바이오엔테크 유에스 인크. Hla 클래스 ii-특이적 에피토프 예측 및 cd4+ t 세포 특징화를 위한 방법 및 시스템
TWI851647B (zh) 2019-01-16 2024-08-11 日商武田藥品工業股份有限公司 用於a型血友病基因治療之編碼表現增加之重組fviii變異體的病毒載體
WO2020160303A1 (fr) 2019-02-01 2020-08-06 Baxalta Incorporated Thérapie génique de l'hémophilie b à l'aide de vecteurs viraux codant pour des variants de fixation recombinants présentant une expression accrue
SG11202109225WA (en) 2019-03-08 2021-09-29 Obsidian Therapeutics Inc Cd40l compositions and methods for tunable regulation
US20230026259A1 (en) 2019-03-08 2023-01-26 Obsidian Therapeutics, Inc. Ca2 compositions and methods for tunable regulation
JP7654557B2 (ja) 2019-03-27 2025-04-01 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア Ｔｎ－ＭＵＣ１キメラ抗原受容体（ＣＡＲ）Ｔ細胞療法
WO2020205889A1 (fr) 2019-04-01 2020-10-08 Tenaya Therapeutics, Inc. Virus adéno-associé comprenant une capside modifiée
US20240124889A1 (en) 2019-05-07 2024-04-18 Voyager Therapeutics, Inc. Compositions and methods for the vectored augmentation of protein destruction, expression and/or regulation
JP7623299B2 (ja) 2019-05-23 2025-01-28 スペースクラフト セブン リミテッド ライアビリティ カンパニー 乳児性悪性大理石骨病に対する遺伝子療法ベクター
WO2020240513A1 (fr) * 2019-05-31 2020-12-03 Avectas Limited Procédés d'administration virale à une population de cellules
US20220226501A1 (en) 2019-05-31 2022-07-21 Universitat Autònoma De Barcelona Insulin gene therapy
EP3980530A1 (fr) 2019-06-07 2022-04-13 Juno Therapeutics, Inc. Culture de lymphocytes t automatisée
WO2020252404A1 (fr) 2019-06-12 2020-12-17 Obsidian Therapeutics, Inc. Compositions de ca2 et procédés de régulation accordable
WO2020252218A1 (fr) 2019-06-12 2020-12-17 Juno Therapeutics, Inc. Combinaison thérapeutique d'une thérapie cytotoxique à médiation cellulaire et d'un inhibiteur d'une protéine de la famille bcl2 pro-survie
KR20220044266A (ko) 2019-06-12 2022-04-07 옵시디안 테라퓨틱스, 인크. 조정 가능한 조절을 위한 ca2 조성물 및 방법
EP3756680A1 (fr) 2019-06-26 2020-12-30 Universitat de Lleida Peptides dérivés de filaments intermédiaires et leurs utilisations
EP3997225A1 (fr) 2019-07-10 2022-05-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Méthodes pour le traitement de l'épilepsie
EP3997226A1 (fr) 2019-07-11 2022-05-18 Tenaya Therapeutics, Inc. Reprogrammation de cellules cardiaques avec des microarn et d'autres facteurs
KR20220066892A (ko) 2019-08-22 2022-05-24 주노 쎄러퓨티크스 인코퍼레이티드 Ｔ 세포 요법 및 제스트 동족체 2의 인핸서 (ｅｚｈ2) 억제제의 병용 요법 및 관련 방법
KR20220073738A (ko) 2019-08-30 2022-06-03 주노 쎄러퓨티크스 인코퍼레이티드 세포 분류를 위한 기계 학습 방법
US20230092895A1 (en) 2019-08-30 2023-03-23 Obsidian Therapeutics, Inc. Tandem cd19 car-based compositions and methods for immunotherapy
US20220333132A1 (en) 2019-09-03 2022-10-20 Sana Blotechnology, Inc. Cd24-associated particles and related methods and uses thereof
WO2021046451A1 (fr) 2019-09-06 2021-03-11 Obsidian Therapeutics, Inc. Compositions et méthodes de régulation de protéine accordable dhfr
US20220332780A1 (en) 2019-09-10 2022-10-20 Obsidian Therapeutics, Inc. Ca2-il15 fusion proteins for tunable regulation
WO2021058795A2 (fr) 2019-09-27 2021-04-01 Stark Labs Domaines de liaison à l'antigène associés à des cellules sénescentes, anticorps et récepteurs antigéniques chimériques les comprenant, et leurs utilisations
EP4041873A4 (fr) 2019-10-08 2023-10-25 Trustees of Boston College Protéines contenant de multiples acides aminés non naturels différents et procédés de fabrication et d'utilisation de telles protéines
US20240122978A1 (en) 2019-10-16 2024-04-18 Umoja Biopharma, Inc. Retroviral vector for univeral receptor therapy
US20220411479A1 (en) 2019-10-30 2022-12-29 Precision Biosciences, Inc. Cd20 chimeric antigen receptors and methods of use for immunotherapy
JP2022554348A (ja) 2019-11-05 2022-12-28 ジュノー セラピューティクス インコーポレイテッド 治療用ｔ細胞組成物の属性を決定する方法
IL292566A (en) 2019-11-05 2022-06-01 Celgene Corp Uses of anti-bcma chimeric antigen receptors
TW202134278A (zh) 2019-11-08 2021-09-16 美商胡曼尼根公司 用於治療腫瘤之ｅｐｈａ３導向ｃａｒ－ｔ細胞
WO2021099394A1 (fr) 2019-11-19 2021-05-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Oligonucléotides antisens et leur utilisation pour le traitement du cancer
WO2021113644A1 (fr) 2019-12-05 2021-06-10 Multivir Inc. Combinaisons comprenant un activateur de lymphocytes t cd8+, un inhibiteur de point de contrôle immunitaire et une radiothérapie en vue d'obtenir des effets ciblés et abscopal pour le traitement du cancer
AU2020395318A1 (en) 2019-12-06 2022-06-09 Juno Therapeutics, Inc. Methods related to toxicity and response associated with cell therapy for treating B cell malignancies
WO2021119357A2 (fr) 2019-12-12 2021-06-17 Baxalta Incorporated Thérapie génique de l'hémophilie à l'aide de vecteurs viraux codant des variants de fviii recombinants présentant une expression accrue
EP4087861A1 (fr) 2020-01-08 2022-11-16 Obsidian Therapeutics, Inc. Compositions et procédés pour la régulation accordable de la transcription
KR20220145341A (ko) 2020-01-24 2022-10-28 주노 쎄러퓨티크스 인코퍼레이티드 입양 세포 요법에서 여포성 림프종 및 변연부 림프종의 투여 및 치료 방법
US20230090117A1 (en) 2020-01-28 2023-03-23 Juno Therapeutics, Inc. Methods for t cell transduction
KR20220144377A (ko) 2020-01-30 2022-10-26 우모자 바이오파마 인코포레이티드 이중특이적 형질도입 촉진제
CN115942950A (zh) 2020-02-04 2023-04-07 Inserm(法国国家健康医学研究院) 治疗炎症性疾病的方法和药物组合物
CA3168337A1 (fr) 2020-02-17 2021-08-26 Marie-Andree Forget Procedes d'expansion de lymphocytes infiltrant les tumeurs et leur utilisation
AR121455A1 (es) 2020-02-28 2022-06-08 Millennium Pharm Inc Método para producir linfocitos citolíticos naturales a partir de citoblastos pluripotentes
US20230103731A1 (en) 2020-03-02 2023-04-06 Tenaya Therapeutics, Inc. Gene vector control by cardiomyocyte-expressed micrornas
JP2023517011A (ja) 2020-03-05 2023-04-21 ネオティーエックス セラピューティクス リミテッド 免疫細胞を用いて癌を治療するための方法および組成物
JP2023516789A (ja) 2020-03-09 2023-04-20 ヤンセン バイオテツク，インコーポレーテツド 組換えベクター核酸の統合を定量化するための組成物及び方法
MX2022011080A (es) 2020-03-10 2023-01-04 Massachusetts Inst Technology Metodos para generar celulas nk de tipo memoria modificadas y composiciones de las mismas.
KR20220153604A (ko) 2020-03-11 2022-11-18 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 가공된 바이러스 입자를 사용하는 유전자 전달을 위한 방법 및 조성물
EP4121115A1 (fr) 2020-03-19 2023-01-25 Trizell Ltd. Système de stockage de virus sensible à la température
EP4125943A1 (fr) 2020-03-27 2023-02-08 Mendus B.V. Utilisation in vivo de cellules modifiées d'origine leucémique pour améliorer l'efficacité d'une thérapie cellulaire adoptive
EP4127139A1 (fr) 2020-03-27 2023-02-08 Mendus B.V. Utilisation ex vivo de cellules modifiées d'origine leucémique pour améliorer l'efficacité d'une thérapie cellulaire adoptive
US20210353543A1 (en) 2020-03-31 2021-11-18 Sana Biotechnology, Inc. Targeted lipid particles and compositions and uses thereof
KR20230005192A (ko) 2020-04-02 2023-01-09 다케다 야쿠힌 고교 가부시키가이샤 Adamts13 변이체, 조성물 및 그의 용도
BR112022020444A2 (pt) 2020-04-10 2022-11-29 Sola Biosciences Llc Composições e métodos para o tratamento de distúrbios de agregação de proteínas
IL297147A (en) 2020-04-10 2022-12-01 Juno Therapeutics Inc Methods and Uses Related to Transgenic Cell Therapy with a Chimeric Antigen Receptor Directed to a B-Cell Maturation Antigen
CN115836130A (zh) 2020-04-27 2023-03-21 朱诺治疗学股份有限公司 聚乙烯亚胺-脱氧核糖核酸复合物大小和活性的稳定化
WO2021222168A2 (fr) 2020-04-28 2021-11-04 Sola Biosciences Llc Compositions et méthodes pour le traitement de protéinopathies tdp-43
US20230178239A1 (en) 2020-05-13 2023-06-08 Juno Therapeutics, Inc. Methods of identifying features associated with clinical response and uses thereof
US20230190871A1 (en) 2020-05-20 2023-06-22 Sana Biotechnology, Inc. Methods and compositions for treatment of viral infections
KR20230017845A (ko) 2020-05-26 2023-02-06 유니버시타트 아우토노마 데 바르셀로나 중추 신경계 장애에 대한 섬유아세포 성장 인자 21(fgf21) 유전자 요법
IL298558A (en) 2020-05-27 2023-01-01 Antion Biosciences Sa Adapter molecules to re-direct car t cells to an antigen of interest
JP2023528377A (ja) 2020-05-29 2023-07-04 フジフィルム セルラー ダイナミクス，インコーポレイテッド 網膜色素上皮及び光受容体の二重細胞凝集体、並びにその使用方法
AU2021280332A1 (en) 2020-05-29 2022-12-01 FUJIFILM Cellular Dynamics, Inc. Bilayer of retinal pigmented epithelium and photoreceptors and use thereof
JP2023529371A (ja) 2020-06-05 2023-07-10 ソラ・バイオサイエンシズ・エルエルシー シヌクレイノパチーの処置のための組成物および方法
US20230265211A1 (en) 2020-06-29 2023-08-24 Inserm (Institut National De La Santé Et De Ls Recherche Médicale) Anti-protein s single-domain antibodies and polypeptides comprising thereof
CN116113697A (zh) 2020-07-10 2023-05-12 国家健康与医学研究院 用于治疗癫痫的方法和组合物
US20230272039A1 (en) 2020-07-16 2023-08-31 Umoja Biopharma, Inc. Gated adapter targeting receptor
EP4192875A1 (fr) 2020-08-10 2023-06-14 Precision BioSciences, Inc. Anticorps et fragments spécifiques de l'antigène de maturation des lymphocytes b et leurs utilisations
EP4196493A1 (fr) 2020-08-13 2023-06-21 A2 Biotherapeutics, Inc. Fusions de gènes pour le contrôle de cellules génétiquement modifiées
EP4204447A1 (fr) 2020-08-28 2023-07-05 Sana Biotechnology, Inc. Agents de liaison anti-viraux modifiés
GB202013940D0 (en) 2020-09-04 2020-10-21 Synpromics Ltd Regulatory nucleic acid sequences
WO2022060806A1 (fr) 2020-09-16 2022-03-24 Obsidian Therapeutics, Inc. Compositions et procédés pour l'expression de récepteurs antigéniques chimériques anti-bcma ayant une il15 régulée par petites molécules dans des cellules t
WO2022076556A2 (fr) 2020-10-07 2022-04-14 Asklepios Biopharmaceutical, Inc. Administration thérapeutique de virus adéno-associé de protéine liée à la fukutine (fkrp) pour le traitement de troubles de la dystroglycanopathie comprenant des ceintures 2i (lgmd2i)
US11781156B2 (en) 2020-10-09 2023-10-10 Tenaya Therapeutics, Inc. Plakophillin-2 gene therapy methods and compositions
EP4232462A1 (fr) 2020-10-26 2023-08-30 SOLA Biosciences LLC Compositions et méthodes pour le traitement de la maladie d'alzheimer
WO2022098685A2 (fr) 2020-11-04 2022-05-12 Celgene Corporation Traitement par les lymphocytes car-t chez des patients ayant reçu un traitement anticancéreux antérieur par un agent alkylant
JP2023547520A (ja) 2020-11-05 2023-11-10 メンドゥス・ベスローテン・フェンノートシャップ 免疫療法における腫瘍非依存性抗原の使用
IL302728A (en) 2020-11-13 2023-07-01 Catamaran Bio Inc Genetically modified natural killer cells and methods of use thereof
US20220162288A1 (en) 2020-11-25 2022-05-26 Catamaran Bio, Inc. Cellular therapeutics engineered with signal modulators and methods of use thereof
US20240016936A1 (en) 2020-12-04 2024-01-18 Celgene Corporation Uses of chimeric antigen receptor (car) t-cell therapies in combination with inhibitors of inflammation-related soluble factors
WO2022125793A1 (fr) 2020-12-10 2022-06-16 Sarepta Therapeutics, Inc. Multiplication par séries de semences en mode suspension pour cellules adhérentes
WO2022132596A2 (fr) 2020-12-14 2022-06-23 Biontech Us Inc. Antigènes spécifiques de tissu pour une immunothérapie anticancéreuse
WO2022133030A1 (fr) 2020-12-16 2022-06-23 Juno Therapeutics, Inc. Polythérapie de thérapie cellulaire et d'inhibiteur de bcl2
CA3204161A1 (fr) 2021-01-11 2022-07-14 Jagesh Vijaykumar SHAH Utilisation de vecteurs viraux ciblant cd8
KR20230143150A (ko) 2021-01-27 2023-10-11 우모자 바이오파마 인코포레이티드 항-cd19 키메라 항원 수용체를 발현하는 세포를 생성하기 위한 렌티바이러스
WO2022162067A1 (fr) 2021-01-30 2022-08-04 Universitat Autònoma De Barcelona Thérapie génique pour le diabète monogène
JP2024510989A (ja) 2021-03-12 2024-03-12 メンドゥス・ベスローテン・フェンノートシャップ ワクチン接種方法及びｃｄ４７遮断薬の使用
TW202304960A (zh) 2021-03-19 2023-02-01 英商葛蘭素史密斯克藍智慧財產發展有限公司 靶向claudin-3之嵌合抗原受體及治療癌症之方法
WO2022204070A1 (fr) 2021-03-22 2022-09-29 Juno Therapeutics, Inc. Procédés de détermination de la puissance d'une composition de cellules thérapeutiques
AU2022244229A1 (en) 2021-03-22 2023-09-14 Juno Therapeutics, Inc. Method to assess potency of viral vector particles
US20240181052A1 (en) 2021-03-29 2024-06-06 Juno Therapeutics, Inc. Methods for dosing and treatment with a combination of a checkpoint inhibitor therapy and a car t cell therapy
WO2022221462A1 (fr) 2021-04-13 2022-10-20 Kriya Therapeutics, Inc. Constructions de vecteur pour l'administration d'acides nucléiques codant pour une vlcad ou une mcad thérapeutique et leurs procédés d'utilisation
AU2022257093A1 (en) 2021-04-16 2023-11-02 Celgene Corporation T cell therapy in patients who have had prior stem cell transplant
KR20240005837A (ko) 2021-05-03 2024-01-12 아스텔라스 인스티튜트 포 리제너러티브 메디슨 성숙한 각막 내피 세포의 생성 방법
CA3217862A1 (fr) 2021-05-05 2022-11-10 Radius Pharmaceuticals, Inc. Modele animal ayant une recombinaison homologue du recepteur pth1 de souris
US20240262917A1 (en) 2021-05-06 2024-08-08 Dana-Farber Cancer Institute, Inc. Antibodies against alk and methods of use thereof
TW202309268A (zh) 2021-05-07 2023-03-01 安斯泰來再生醫藥協會 產生成熟肝細胞的方法
EP4089171A1 (fr) 2021-05-12 2022-11-16 Fundación del Sector Público Estatal Centro Nacional de Investigaciones Oncológicas Carlos III (F.S.P. CNIO) Génomes et vecteurs viraux recombinants à encodage tert
EP4347619A2 (fr) 2021-05-26 2024-04-10 Institut National de la Santé et de la Recherche Médicale (INSERM) Peptides dérivés d'hexokinase et leurs utilisations thérapeutiques
WO2022251443A1 (fr) 2021-05-26 2022-12-01 FUJIFILM Cellular Dynamics, Inc. Procédés pour empêcher le silençage rapide de gènes dans des cellules souches pluripotentes
EP4347620A1 (fr) 2021-05-28 2024-04-10 Sana Biotechnology, Inc. Particules lipidiques contenant une glycoprotéine d'enveloppe de rétrovirus endogène de babouin (baev) tronquée et méthodes et utilisations associées
WO2022258606A1 (fr) 2021-06-07 2022-12-15 Gadeta B.V. Chaînes de récepteurs de lymphocytes t delta ou de lymphocytes t gamma ou parties associées induisant une réponse antitumorale ou anti-infectieuse
JP2024527252A (ja) 2021-06-14 2024-07-24 武田薬品工業株式会社 発現の増加した組み換えｆｖｉｉｉバリアントをコードするウイルスベクターを用いた、血友病ａの遺伝子療法
WO2022263407A2 (fr) 2021-06-14 2022-12-22 INSERM (Institut National de la Santé et de la Recherche Médicale) Polypeptides d'annexine a5 mutants et leurs utilisations à des fins thérapeutiques
CN117813374A (zh) 2021-06-15 2024-04-02 武田药品工业株式会社 从多能干细胞产生自然杀伤细胞的方法
WO2023278811A1 (fr) 2021-07-01 2023-01-05 Indapta Therapeutics, Inc. Cellules tueuses naturelles (nk) modifiées et méthodes associées
AU2022310862A1 (en) 2021-07-14 2024-02-01 Regeneron Pharmaceuticals, Inc. Engineered t cell receptors fused to binding domains from antibodies
AU2022312170A1 (en) 2021-07-16 2024-02-08 Academisch Ziekenhuis Leiden H.O.D.N. Lumc Oligonucleotide for inhibiting quaking activity
EP4380967A1 (fr) 2021-08-04 2024-06-12 The Regents of the University of Colorado, a body corporate Cellules t de récepteur d'antigène chimérique activant le lat et leurs méthodes d'utilisation
US20240344083A1 (en) 2021-08-04 2024-10-17 Sana Biotechnology, Inc. Use of cd4-targeted viral vectors
AU2022324621A1 (en) 2021-08-06 2024-01-18 Celgene Corporation Compositions and methods for selective degradation of engineered proteins
CA3227108A1 (fr) 2021-08-11 2023-02-16 Xiaomeng HU Cellules primaires genetiquement modifiees pour une therapie cellulaire allogenique
AU2022325955A1 (en) 2021-08-11 2024-02-08 Sana Biotechnology, Inc. Genetically modified cells for allogeneic cell therapy to reduce instant blood mediated inflammatory reactions
WO2023019226A1 (fr) 2021-08-11 2023-02-16 Sana Biotechnology, Inc. Cellules génétiquement modifiées pour une thérapie cellulaire allogénique
AU2022325231A1 (en) 2021-08-11 2024-02-08 Sana Biotechnology, Inc. Genetically modified cells for allogeneic cell therapy to reduce complement-mediated inflammatory reactions
US20240216432A1 (en) 2021-08-16 2024-07-04 Hemogenyx Pharmaceuticals Llc Anti-flt3 antibodies, cars, car t cells and methods of use
US20240400626A1 (en) 2021-10-08 2024-12-05 Sola Biosciences Llc Compositions and methods for the treatment of p53-mediated cancers
EP4413024A2 (fr) 2021-10-08 2024-08-14 SOLA Biosciences LLC Compositions et méthodes de traitement de protéopathies
WO2023077107A1 (fr) 2021-10-29 2023-05-04 Sana Biotechnology, Inc. Procédés et réactifs pour amplifier des produits d'acide nucléique de vecteur viral
US20250041339A1 (en) 2021-11-19 2025-02-06 The Trustees Of The University Of Pennsylvania Engineered Pan-Leukocyte Antigen CD45 to Facilityate CAR T Cell Therapy
US20250059560A1 (en) 2021-12-16 2025-02-20 Sana Biotechnology, Inc. Methods and systems of particle production
US20250051755A1 (en) 2021-12-17 2025-02-13 Dana-Farber Cancer Institute, Inc. Platform for antibody discovery
US20250041415A1 (en) 2021-12-17 2025-02-06 Umoja Biopharma, Inc. Cytotoxic innate lymphoid cell and uses thereof
EP4448549A2 (fr) 2021-12-17 2024-10-23 Sana Biotechnology, Inc. Glycoprotéines de fusion de paramyxoviridae modifiées
TW202342757A (zh) 2021-12-17 2023-11-01 美商薩那生物科技公司 經修飾副黏液病毒科附著醣蛋白
WO2023114544A1 (fr) 2021-12-17 2023-06-22 Dana-Farber Cancer Institute, Inc. Anticorps et leurs utilisations
US20250082777A1 (en) 2022-01-10 2025-03-13 Sana Biotechnology, Inc. Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses
CN119013393A (zh) 2022-01-28 2024-11-22 朱诺治疗学股份有限公司 制造细胞组合物的方法
US20250152709A1 (en) 2022-02-01 2025-05-15 Sana Biotechnology, Inc. Cd3-targeted lentiviral vectors and uses thereof
US20250144235A1 (en) 2022-02-02 2025-05-08 Sana Biotechnology, Inc. Methods of repeat dosing and administration of lipid particles or viral vectors and related systems and uses
EP4479416A1 (fr) 2022-02-17 2024-12-25 Sana Biotechnology, Inc. Protéines cd47 modifiées et leurs utilisations
WO2023172514A1 (fr) 2022-03-07 2023-09-14 Catamaran Bio, Inc. Agents thérapeutiques de cellules immunitaires modifiés ciblés sur her2 et leurs procédés d'utilisation
JP2025508041A (ja) 2022-03-09 2025-03-21 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド 遺伝子操作されたｂ細胞及びその使用方法
WO2023173123A1 (fr) 2022-03-11 2023-09-14 Sana Biotechnology, Inc. Cellules génétiquement modifiées et compositions et utilisations associées
AU2023236826A1 (en) 2022-03-18 2024-09-26 The Regents Of The University Of Colorado, A Body Corporate Genetically engineered t-cell co-receptors and methods of use thereof
WO2023193015A1 (fr) 2022-04-01 2023-10-05 Sana Biotechnology, Inc. Polythérapies d'agoniste de récepteur de cytokine et de vecteur viral
EP4504249A2 (fr) 2022-04-08 2025-02-12 Regeneron Pharmaceuticals, Inc. Récepteur multipartite et complexes de signalisation
WO2023212683A1 (fr) 2022-04-29 2023-11-02 Kriya Therapeutics, Inc. Compositions de thérapie génique de l'insuline et de la glucokinase et leur utilisation pour le traitement du diabète
GB202206507D0 (en) 2022-05-04 2022-06-15 Antion Biosciences Sa Expression construct
EP4522183A2 (fr) 2022-05-11 2025-03-19 Celgene Corporation Méthodes et utilisations associées à une thérapie par lymphocytes t et leur production
US20240002800A1 (en) 2022-05-16 2024-01-04 Mendus B.V. Use of leukemia-derived cells for enhancing natural killer (nk) cell therapy
CN119562820A (zh) 2022-05-17 2025-03-04 优莫佳生物制药股份有限公司 制造病毒颗粒
EP4526455A1 (fr) 2022-05-18 2025-03-26 The Children's Hospital of Philadelphia Compositions et procédés de régulation de l'épissage alternatif inductible de l'expression génique
WO2023227594A1 (fr) 2022-05-24 2023-11-30 Gadeta Bv Nouvelles chaînes de récepteurs de cellules t delta et chaînes de récepteurs de cellules t gamma ou parties de celles-ci
WO2023230548A1 (fr) 2022-05-25 2023-11-30 Celgene Corporation Procédé de prédiction d'une réponse à une thérapie par lymphocyte t
AU2023275764A1 (en) 2022-05-26 2024-12-05 Regeneron Pharmaceuticals, Inc. Compositions for maintaining lentiviral vector and uses thereof
WO2023237541A1 (fr) 2022-06-07 2023-12-14 Gadeta B.V. Chaînes de récepteurs de lymphocytes t delta ou de lymphocytes t gamma ou des parties de celles-ci qui médient une réponse anti-tumorale ou anti-infectieuse
WO2023237663A1 (fr) 2022-06-09 2023-12-14 Institut National de la Santé et de la Recherche Médicale Utilisation du variant irf4 faux sens f359l pour augmenter la stabilité de lymphocytes t régulateurs
IL317532A (en) 2022-06-10 2025-02-01 Umoja Biopharma Inc Engineered stem cells and their uses
KR20250029137A (ko) 2022-06-22 2025-03-04 주노 쎄러퓨티크스 인코퍼레이티드 Cd19-표적화된 car t 세포의 2차 요법을 위한 치료 방법
EP4547824A1 (fr) 2022-06-29 2025-05-07 Fujifilm Holdings America Corporation Astrocytes dérivés d'ipsc et leurs procédés d'utilisation
WO2024007020A1 (fr) 2022-06-30 2024-01-04 Indapta Therapeutics, Inc. Combinaison de cellules tueuses naturelles (nk) modifiées et d'une thérapie par anticorps et méthodes associées
WO2024015892A1 (fr) 2022-07-13 2024-01-18 The Broad Institute, Inc. Procédés et systèmes faisant intervenir l'immunopeptidome hla-ii pour la découverte d'antigènes
WO2024013401A1 (fr) 2022-07-15 2024-01-18 Gadeta B.V. Nouveau procédé d'identification de chaînes de récepteurs de lymphocytes t gamma (ou de lymphocytes t delta) (ou récepteurs de lymphocytes t gammadelta) ou de leurs fragments qui médient une réponse anti-tumorale ou anti-infectieuse
WO2024018003A1 (fr) 2022-07-21 2024-01-25 Institut National de la Santé et de la Recherche Médicale Vésicules extracellulaires fonctionnalisées avec une syncytine d'erv et leurs utilisations pour l'administration de charge
WO2024017990A1 (fr) 2022-07-21 2024-01-25 Institut National de la Santé et de la Recherche Médicale Méthodes et compositions pour le traitement de troubles de la douleur chronique
WO2024026377A1 (fr) 2022-07-27 2024-02-01 Sana Biotechnology, Inc. Procédés de transduction utilisant un vecteur viral et des inhibiteurs de facteurs de restriction antiviraux
WO2024031060A1 (fr) 2022-08-04 2024-02-08 Elevatebio Technologies, Inc. Vecteurs lentiviraux et leurs utilisations
TW202416993A (zh) 2022-08-15 2024-05-01 瑞士商赫孚孟拉羅股份公司 預防或減輕與重組病毒載體相關的不良反應
WO2024044655A1 (fr) 2022-08-24 2024-02-29 Sana Biotechnology, Inc. Administration de protéines hétérologues
WO2024047110A1 (fr) 2022-08-31 2024-03-07 Institut National de la Santé et de la Recherche Médicale Procédé de génération de cellules car-t plus efficaces
WO2024052318A1 (fr) 2022-09-06 2024-03-14 Institut National de la Santé et de la Recherche Médicale Nouvelles cellules car-t à double division destinées au traitement de malignités hématologiques cd38-positives
WO2024052413A1 (fr) 2022-09-07 2024-03-14 Universitat Autònoma De Barcelona Vecteurs de beta-hexosaminidase
WO2024064838A1 (fr) 2022-09-21 2024-03-28 Sana Biotechnology, Inc. Particules lipidiques comprenant des glycoprotéines fixant des paramyxovirus variants et leurs utilisations
WO2024081820A1 (fr) 2022-10-13 2024-04-18 Sana Biotechnology, Inc. Particules virales ciblant des cellules souches hématopoïétiques
TW202434621A (zh) 2022-11-04 2024-09-01 美商優莫佳生物製藥有限公司 多核苷酸構築體及相關病毒載體及方法
WO2024098028A2 (fr) 2022-11-04 2024-05-10 Umoja Biopharma, Inc. Particules lentivirales affichant des molécules de fusion et leurs utilisations
WO2024097992A2 (fr) 2022-11-04 2024-05-10 Umoja Biopharma, Inc. Particules présentant des fusions de molécules d'adhésion
WO2024100136A1 (fr) 2022-11-08 2024-05-16 Gadeta B.V. Nouveau procédé d'obtention de chaînes de récepteurs de lymphocytes t gamma (ou de lymphocytes t delta) (ou de récepteurs de lymphocytes t gamma delta) ou de fragments de ceux-ci qui médient une réponse antitumorale ou anti-infectieuse
WO2024119157A1 (fr) 2022-12-02 2024-06-06 Sana Biotechnology, Inc. Particules lipidiques avec cofusogènes et leurs procédés de production et d'utilisation
WO2024129696A1 (fr) 2022-12-12 2024-06-20 Retromer Therapeutics Corp. Constructions lentivirales et aav comprenant un mini-gène sorl1 destiné à être utilisé dans le traitement de maladies neurodégénératives
WO2024146935A1 (fr) 2023-01-06 2024-07-11 Institut National de la Santé et de la Recherche Médicale Administration intraveineuse d'oligonucléotides antisens pour le traitement de la douleur
WO2024151541A1 (fr) 2023-01-09 2024-07-18 Sana Biotechnology, Inc. Souris auto-immune présentant un diabète de type 1
WO2024170500A1 (fr) 2023-02-13 2024-08-22 Institut National de la Santé et de la Recherche Médicale Méthodes de traitement de maladies liées à une carence en fer
WO2024178386A1 (fr) 2023-02-24 2024-08-29 Aarhus Universitet Méthodes de traitement des maladies du trafic endosomal
WO2024206928A1 (fr) 2023-03-30 2024-10-03 Pharma Cinq, Llc Vecteur codant un facteur de viabilité de cône dérivé de tige et séquence de signal igk humain
WO2024209036A1 (fr) 2023-04-07 2024-10-10 Institut National de la Santé et de la Recherche Médicale Génération de populations neuronales glutamatergiques de haute pureté par l'utilisation du facteur pro-neural ascl1
WO2024213767A1 (fr) 2023-04-14 2024-10-17 Institut National de la Santé et de la Recherche Médicale Greffe de cellules stromales mésenchymateuses conçues pour stimuler l'infiltration immunitaire dans les tumeurs
WO2024220588A1 (fr) 2023-04-18 2024-10-24 Juno Therapeutics, Inc. Essai cytotoxique pour évaluer la puissance de compositions de cellules thérapeutiques
WO2024220574A1 (fr) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Fusogènes de protéine g universelle et systèmes adaptateurs de ceux-ci et particules lipidiques et utilisations associées
WO2024220597A2 (fr) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Dosage numérique utilisant des gouttelettes pour détecter un vecteur lentiviral compétent pour la réplication
WO2024220560A1 (fr) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Fusogènes de protéine g modifiés et particules lipidiques associées et procédés associés
WO2024218341A1 (fr) 2023-04-19 2024-10-24 Glaxosmithkline Intellectual Property Development Limited Chimères ciblant la cytotoxicité pour cellules car-t et car-nk
WO2024226858A1 (fr) 2023-04-26 2024-10-31 Juno Therapeutics, Inc. Procédés de fabrication de vecteurs viraux
WO2024229302A1 (fr) 2023-05-03 2024-11-07 Sana Biotechnology, Inc. Procédés de dosage et d'administration de cellules d'îlots modifiées
GB202306619D0 (en) 2023-05-04 2023-06-21 Antion Biosciences Sa Cell
WO2024231820A1 (fr) 2023-05-05 2024-11-14 Takeda Pharmaceutical Company Limited Traitement de la maladie de pompe
WO2024238153A1 (fr) 2023-05-15 2024-11-21 Umoja Biopharma, Inc. Administration lentivirale de récepteurs antigéniques chimériques anti-cd20
WO2024243236A2 (fr) 2023-05-22 2024-11-28 Sana Biotechnology, Inc. Procédés d'administration de cellules des îlots pancréatiques et procédés associés
WO2024243340A1 (fr) 2023-05-23 2024-11-28 Sana Biotechnology, Inc. Fusogènes en tandem et particules lipidiques associées
WO2024243365A2 (fr) 2023-05-23 2024-11-28 Juno Therapeutics, Inc. Marqueurs d'activation de lymphocytes t et procédé d'évaluation de l'activation de lymphocytes t
WO2025004002A2 (fr) 2023-06-30 2025-01-02 Takeda Pharmaceutical Company Limited Traitement de la maladie de pompe
WO2025008406A1 (fr) 2023-07-04 2025-01-09 Institut National de la Santé et de la Recherche Médicale Oligonucléotides antisens et leur utilisation pour le traitement du cancer
WO2025008774A1 (fr) 2023-07-05 2025-01-09 Takeda Pharmaceutical Company Limited Vecteurs viraux codant pour des variants de fviii recombinants ayant une expression accrue pour la thérapie génique de l'hémophilie a
WO2025017186A1 (fr) 2023-07-20 2025-01-23 Institut National de la Santé et de la Recherche Médicale Vésicules extracellulaires fonctionnalisées avec un système d'attache pour l'administration de molécules cargo
WO2025032112A1 (fr) 2023-08-08 2025-02-13 Institut National de la Santé et de la Recherche Médicale Méthodes de traitement de maladies médiées par type 2
WO2025049905A1 (fr) 2023-09-01 2025-03-06 Gennao Bio, Inc. Co-expression de dnase dans des cellules hôtes
WO2025059113A1 (fr) 2023-09-12 2025-03-20 The Board Of Regents Of The University Of Oklahoma Traitements pour améliorer la réponse immunitaire à des infections à clostridioides difficile
WO2025097055A2 (fr) 2023-11-02 2025-05-08 The Broad Institute, Inc. Compositions et méthodes d'utilisation de lymphocytes t en immunothérapie

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5716826A (en) 1988-03-21 1998-02-10 Chiron Viagene, Inc. Recombinant retroviruses
FR2629469B1 (fr) 1988-03-31 1990-12-21 Pasteur Institut Retrovirus recombinant defectif, son application a l'integration de sequences codantes pour des proteines determinees dans le genome de cultures cellulaires infectables par le retrovirus sauvage correspondant et adns recombinants pour la production de ce retrovirus recombinant
US5614404A (en) 1988-06-10 1997-03-25 Theriod Biologics, Incorporated Self-assembled, defective, non-self-propagating lentivirus particles
US5665577A (en) 1989-02-06 1997-09-09 Dana-Farber Cancer Institute Vectors containing HIV packaging sequences, packaging defective HIV vectors, and uses thereof
AU6075190A (en) 1989-06-30 1991-01-17 Regents Of The University Of California, The Retrovirus detection
US5747307A (en) 1992-02-28 1998-05-05 Syngenix Limited Mason-Pfizer Monkey Retroviral packaging defective vectors
US5834256A (en) 1993-06-11 1998-11-10 Cell Genesys, Inc. Method for production of high titer virus and high efficiency retroviral mediated transduction of mammalian cells
US6051427A (en) * 1993-06-11 2000-04-18 Cell Genesys, Inc. Method for production of high titer virus and high efficiency retroviral mediated transduction of mammalian cells
US5589362A (en) 1993-06-14 1996-12-31 Basf Aktiengesellschaft Tetracycline regulated transcriptional modulators with altered DNA binding specificities
US5591579A (en) 1993-12-21 1997-01-07 Washington University Indicator cell line for detecting RNA viruses and method therefor
US5739118A (en) 1994-04-01 1998-04-14 Apollon, Inc. Compositions and methods for delivery of genetic material
AU2419595A (en) 1994-05-10 1995-11-29 Hisamitsu Pharmaceutical Co., Inc. Recombinant human immunodeficiency virus vector and process for producing the same
WO1995032300A1 (fr) * 1994-05-23 1995-11-30 University Of Medicine & Dentistry Of New Jersey Destruction biologique selective des cellules tumorales
US5693508A (en) 1994-11-08 1997-12-02 Chang; Lung-Ji Retroviral expression vectors containing MoMLV/CMV-IE/HIV-TAR chimeric long terminal repeats
US5681746A (en) 1994-12-30 1997-10-28 Chiron Viagene, Inc. Retroviral delivery of full length factor VIII
US5650309A (en) 1995-05-16 1997-07-22 The Regents Of The University Of California Viral vectors
GB9510272D0 (en) 1995-05-22 1995-07-19 Isis Innovation Retroviral vectors
US6013516A (en) 1995-10-06 2000-01-11 The Salk Institute For Biological Studies Vector and method of use for nucleic acid delivery to non-dividing cells
WO1997020052A1 (fr) * 1995-11-28 1997-06-05 Clinical Technologies, Inc. Vih recombine, cellules d'encapsidation modifiees et methode de traitement du syndrome d'immunodeficience acquise
US5750383A (en) 1996-05-14 1998-05-12 Boyce Thompson Institute For Plant Research, Inc. Baculovirus cloning system
AU4261797A (en) 1996-09-17 1998-04-14 Salk Institute For Biological Studies, The Retroviral vectors capable of transducing non-dividing cells
GB9621680D0 (en) * 1996-10-17 1996-12-11 Oxford Biomedica Ltd Lentiviral vectors
HUP0000421A2 (hu) * 1996-10-17 2000-06-28 Oxford Biomedica (Uk) Limited Retrovirális vektorok
US6207455B1 (en) 1997-05-01 2001-03-27 Lung-Ji Chang Lentiviral vectors
JP2001510053A (ja) 1997-07-18 2001-07-31 カイロン コーポレイション レンチウイルスベクター
US5994136A (en) 1997-12-12 1999-11-30 Cell Genesys, Inc. Method and means for producing high titer, safe, recombinant lentivirus vectors
EP1045921A2 (fr) 1998-01-16 2000-10-25 Chiron Corporation Vecteurs de therapie genique du virus de l'immunodeficience feline
EP0949332A3 (fr) * 1998-04-01 2001-03-28 Smithkline Beecham Plc Polypeptides HSSCRG1
ATE367447T1 (de) * 1998-05-13 2007-08-15 Genetix Pharmaceuticals Inc Lentivirale verpackungszellen
IL146144A0 (en) 1999-04-29 2002-07-25 Cell Genesys Inc Method and means for producing high titer, safe, recombinant lentivirus vectors

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BLOMER U, ET AL.: "HIGHLY EFFICIENT AND SUSTAINED GENE TRANSFER IN ADULT NEURONS WITH A LENTIVIRUS VECTOR", JOURNAL OF VIROLOGY., THE AMERICAN SOCIETY FOR MICROBIOLOGY., US, vol. 71, no. 09, 1 September 1997 (1997-09-01), US, pages 6641 - 6649, XP002917174, ISSN: 0022-538X *
ELDER J H, PHILLIPS T R: "FELINE IMMUNODEFICIENCY VIRUS AS A MODEL FOR DEVELOPMENT OF MOLECULAR APPROCHES TO INTERVENTION STRATEGIES AGAINST LENTIVIRUS INFECTIONS", ADVANCES IN VIRUS RESEARCH., SAN DIEGO, CA., US, vol. 45, 1 January 1900 (1900-01-01), US, pages 225 - 247, XP002917175 *
NALDINI L, ET AL.: "EFFICIENT TRANSFER, INTEGRATION, AND SUSTAINED LONG-TERM EXPRESSIONOF THE TRANSGENE IN ADULT RAT BRAINS INJECTED WITH A LENTIVIRAL VECTOR", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, US, vol. 93, 1 October 1996 (1996-10-01), US, pages 11382 - 11388, XP002917173, ISSN: 0027-8424, DOI: 10.1073/pnas.93.21.11382 *
NALDINI L, ET AL.: "IN VIVO GENE DELIVERY AND STABLE TRANSDUCTION OF NONDIVIDING CELLS BY A LENTIVIRAL VECTOR", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 272, 12 April 1996 (1996-04-12), US, pages 263 - 267, XP002917172, ISSN: 0036-8075, DOI: 10.1126/science.272.5259.263 *
See also references of EP1036182A4 *

Cited By (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8846385B2 (en) 1997-12-12 2014-09-30 Gbp Ip, Llc Method and means for producing high titer, safe recombinant lentivirus vectors
US8652837B2 (en) 1999-04-29 2014-02-18 Gbp Ip, Llc Method and means for producing high titer, safe, recombinant lentivirus vectors
JP4979851B2 (ja) * 1999-04-29 2012-07-18 ジービーピー アイピー リミテッド ライアビリティ カンパニー 高いタイターで安全な組換えレンチウイルスベクターの作製方法
EP1849873A1 (fr) * 1999-04-29 2007-10-31 Cell Genesys, Inc. Procédé et supports de production de vecteurs de lentivirus recombinant sécurisé à fort dosage
US7250299B1 (en) 1999-04-29 2007-07-31 Cell Genesys, Inc. Method and means for producing high titer, safe, recombinant lentivirus vectors
EP1171624A4 (fr) * 1999-04-29 2002-06-26 Cell Genesys Inc Procede et moyens de production de vecteurs lentiviraux recombinants surs et a titre eleve
WO2000078987A1 (fr) * 1999-06-22 2000-12-28 Dnavec Research Inc. Vecteur d'expression de deux genes etrangers
US6979568B1 (en) 1999-06-22 2005-12-27 Dnavec Research, Inc. Vector for the expression of two foreign genes
EP1964573A2 (fr) 1999-10-22 2008-09-03 Aventis Pasteur Limited Procédé d'induction et/ou amélioration d'une réponse immune vers des antigènes de tumeurs
EP1741782A2 (fr) 2000-05-10 2007-01-10 Sanofi Pasteur Limited Polypeptides immunogéniques codés par des minigènes mage et leurs utilisations
WO2001091801A3 (fr) * 2000-05-26 2003-02-06 Chiron Corp Procedes de transduction de cellules neuronales cerebelleuses par le biais de vecteurs de lentivirus
US6712612B1 (en) 2000-12-12 2004-03-30 Genecure Llc Safe and stable retroviral helper cell line and related compositions and methods
WO2002049422A3 (fr) * 2000-12-20 2002-11-14 Leuven K U Res & Dev Modeles de maladies developpes chez des animaux non humains
US7179903B2 (en) 2001-05-14 2007-02-20 Cell Genesys, Inc Liver specific transcriptional enhancer
US7745179B2 (en) 2001-05-14 2010-06-29 Gbp Ip, Llc Lentiviral vectors featuring liver specific transcriptional enhancer and methods of using same
US6808905B2 (en) 2001-05-14 2004-10-26 Cell Genesys, Inc. Lentiviral vectors encoding clotting factors for gene therapy
WO2006010834A1 (fr) 2004-06-25 2006-02-02 Centre National De La Recherche Scientifique Lentivirus non integratif et non replicatif, preparation et utilisations
US9593340B2 (en) 2007-10-15 2017-03-14 Admedus Vaccines Pty Ltd. Expression system for modulating an immune response
US9795658B2 (en) 2010-04-20 2017-10-24 Admedus Vaccines Pty Ltd Expression system for modulating an immune response
US11787851B2 (en) 2013-02-15 2023-10-17 Bioverativ Therapeutics Inc. Optimized factor VIII gene
US12275970B2 (en) 2014-06-30 2025-04-15 Bioverativ Therapeutics Inc. Optimized factor IX gene
US11008561B2 (en) 2014-06-30 2021-05-18 Bioverativ Therapeutics Inc. Optimized factor IX gene
WO2017096432A1 (fr) 2015-12-09 2017-06-15 Admedus Vaccines Pty Ltd Composition immunomodulatrice pour le traitement
WO2017136358A1 (fr) 2016-02-01 2017-08-10 Bioverativ Therapeutics Inc. Gènes du facteur viii optimisés
US11753461B2 (en) 2016-02-01 2023-09-12 Bioverativ Therapeutics Inc. Optimized factor VIII genes
EP4137570A1 (fr) 2016-02-01 2023-02-22 Bioverativ Therapeutics Inc. Gènes du facteur viii optimisés
US11446398B2 (en) 2016-04-11 2022-09-20 Obsidian Therapeutics, Inc. Regulated biocircuit systems
US11285191B2 (en) 2016-07-26 2022-03-29 The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Immunostimulatory compositions and uses therefor
WO2018071676A1 (fr) 2016-10-12 2018-04-19 Bioverativ Usa Inc. Anticorps anti-c1s et leurs méthodes d'utilisation
US11332521B2 (en) 2016-11-07 2022-05-17 Neuracle Science Co., Ltd. Anti-family with sequence similarity 19, member A5 antibodies and method of use thereof
WO2018083538A1 (fr) 2016-11-07 2018-05-11 Neuracle Scienc3 Co., Ltd. Anticorps anti- famille avec similarité de séquence 19, élément a5 et leur procédé d'utilisation
US12202889B2 (en) 2016-11-07 2025-01-21 Neuracle Science Co., Ltd. Anti-family with sequence similarity 19, member A5 antibodies and method of use thereof
US12077579B2 (en) 2017-06-27 2024-09-03 Neuracle Science Co., Ltd. Use of anti-FAM19A5 antibodies for treating fibrosis
US11618783B2 (en) 2017-06-27 2023-04-04 Neuracle Science Co., Ltd. Anti-FAM19A5 antibodies and uses thereof
US11155613B2 (en) 2017-06-27 2021-10-26 Neuracle Science Co., Ltd. Use of anti-FAM19A5 antibodies for treating fibrosis
US11746149B2 (en) 2017-06-27 2023-09-05 Neuracle Science Co., Ltd. Use of anti-family with sequence similarity 19, member A5 antibodies for the treatment of glaucoma
US11560425B2 (en) 2017-06-27 2023-01-24 Neuracle Science Co., Ltd. Use of anti-FAM19A5 antibodies for treating cancers
WO2019075220A1 (fr) 2017-10-11 2019-04-18 Bioverativ Usa Inc. Procédés permettant d'induire une activité de complément
WO2019152692A1 (fr) 2018-02-01 2019-08-08 Bioverativ Therapeutics, Inc. Utilisation de vecteurs lentiviraux exprimant le facteur viii
US11634484B2 (en) 2018-04-24 2023-04-25 Neuracle Science Co., Ltd. Use of anti-family with sequence similarity 19, member A5 antibodies for the treatment of neuropathic pain
US11970532B2 (en) 2018-05-10 2024-04-30 Neuracle Science Co., Ltd. Anti-family with sequence similarity 19, member A5 antibodies and method of use thereof
US11884729B2 (en) 2018-06-29 2024-01-30 ApitBio, Inc Anti-L1CAM antibodies and uses thereof
WO2020102728A1 (fr) 2018-11-16 2020-05-22 Neoimmunetech, Inc. Méthode de traitement d'une tumeur au moyen de l'association de la protéine il-7 et d'un inhibiteur de point de contrôle immunitaire
WO2020118069A2 (fr) 2018-12-06 2020-06-11 Bioverativ Therapeutics Inc. Utilisation de vecteurs lentiviraux exprimant le facteur ix
WO2020123377A1 (fr) 2018-12-10 2020-06-18 Neoimmunetech, Inc. Cellules défaillantes nrf-2 et utilisations de celles-ci
US12247070B2 (en) 2018-12-27 2025-03-11 Neuracle Science Co., Ltd. Use of anti-FAM19A5 antibodies for treating atherosclerosis
WO2021067389A1 (fr) 2019-09-30 2021-04-08 Bioverativ Therapeutics Inc. Formulations de vecteur lentiviral
WO2021146191A1 (fr) 2020-01-13 2021-07-22 Neoimmunetech, Inc. Procédé de traitement d'une tumeur au moyen d'une combinaison d'une protéine il-7 et d'un anticorps bispécifique
WO2021151001A1 (fr) 2020-01-22 2021-07-29 Outpace Bio, Inc. Polypeptides chimères
WO2021151006A2 (fr) 2020-01-22 2021-07-29 Outpace Bio, Inc. Polypeptides chimériques
WO2021158783A1 (fr) 2020-02-05 2021-08-12 Washington University Procédé de traitement d'une tumeur solide avec une combinaison d'une protéine d'il-7 et de cellules immunitaires porteuses de car
WO2021262963A1 (fr) 2020-06-24 2021-12-30 Bioverativ Therapeutics Inc. Procédés pour retirer le facteur viii à l'état libre contenu dans des préparations de vecteurs lentiviraux modifiés pour exprimer ladite protéine
US12173307B2 (en) 2020-06-24 2024-12-24 Bioverativ Therapeutics Inc. Methods for the purification of viral vectors
WO2022087453A1 (fr) 2020-10-22 2022-04-28 Lyell Immunopharma, Inc. Récepteurs d'activation chimériques
WO2022093718A1 (fr) 2020-10-26 2022-05-05 Neoimmunetech, Inc. Procédés d'induction de la mobilisation de cellules souches
WO2022094475A1 (fr) 2020-11-02 2022-05-05 Neoimmunetech, Inc. Utilisation de l'interleukine-7 pour le traitement du coronavirus
WO2022099022A1 (fr) 2020-11-05 2022-05-12 Neoimmunetech, Inc. Procédé de traitement d'une tumeur au moyen d'une combinaison d'une protéine il-7 et d'un vaccin nucléotidique
WO2022251644A1 (fr) 2021-05-28 2022-12-01 Lyell Immunopharma, Inc. Cellules immunitaires déficientes en nr4a3 et leurs utilisations
WO2022256437A1 (fr) 2021-06-02 2022-12-08 Lyell Immunopharma, Inc. Cellules immunitaires déficientes en nr4a3 et leurs utilisations
WO2023056331A1 (fr) 2021-09-30 2023-04-06 Bioverativ Therapeutics Inc. Acides nucléiques codant pour des polypeptides du facteur viii à immunogénicité réduite
WO2023081923A1 (fr) 2021-11-08 2023-05-11 Frequency Therapeutics, Inc. Inhibiteurs du récepteur du facteur de croissance dérivé des plaquettes (pdgfr) alpha et leurs utilisations
WO2023130081A1 (fr) 2021-12-30 2023-07-06 Neoimmunetech, Inc. Procédé de traitement d'une tumeur avec une combinaison d'une protéine il-7 et d'un antagoniste du vegf
WO2024026490A1 (fr) 2022-07-28 2024-02-01 Sqz Biotechnologies Company Polynucléotides codant pour des antigènes liés et leurs utilisations
WO2024102722A1 (fr) 2022-11-07 2024-05-16 Neoimmunetech, Inc. Procédés de traitement d'une tumeur avec un promoteur mgmt non méthylé
WO2025010272A1 (fr) 2023-07-03 2025-01-09 Neoimmunetech, Inc. Molécules fc hétérodimères et leurs utilisations

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US6165782A (en) 2000-12-26
CA2314609A1 (fr) 1999-06-24
DE69838758D1 (de) 2008-01-03
EP1036182A1 (fr) 2000-09-20
JP4640742B2 (ja) 2011-03-02
DE69838758T2 (de) 2008-10-30
AU1803499A (en) 1999-07-05
EP1036182B1 (fr) 2007-11-21
US20020173030A1 (en) 2002-11-21
US7083981B2 (en) 2006-08-01
US5994136A (en) 1999-11-30
US8846385B2 (en) 2014-09-30
US6924144B2 (en) 2005-08-02
EP1036182A4 (fr) 2004-10-06
JP2002508184A (ja) 2002-03-19
US20080286836A1 (en) 2008-11-20
WO1999031251A9 (fr) 1999-10-07
US20050255597A1 (en) 2005-11-17
US6428953B1 (en) 2002-08-06
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KR20010033064A (ko) 2001-04-25
CA2314609C (fr) 2014-07-08

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